Advanced Malignant Solid NeoplasmPhase 1NCT02419495
Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies
A Phase 1 study testing Capecitabine, Carboplatin and Cyclophosphamide in people with Advanced Malignant Solid Neoplasm and Clinical Stage III Cutaneous Melanoma AJCC v8, run by M.D. Anderson Cancer Center at 5 sites in United States.
Trial summary
This phase Ib trial studies the side effects and best dose of selinexor when given together with several different standard chemotherapy or immunotherapy regimens in treating patients with malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8
- What is being tested?
- Capecitabine, Carboplatin and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 221 participants
- Where
- 5 sitesUnited States
- Study dates
- 26 Jun 2015to 16 Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment; patients in Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) that have Food and Drug Administration (FDA)-approved indications for nivolumab, ipilimumab, and pembrolizumab do not have to fail first line nivolumab, ipilimumab, or pembrolizumab, and these patients may be treatment naïve if they have disease where pembrolizumab or nivolumab are FDA approved for the first-line setting
- For all arms except Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) patients must have failed prior standard curative chemotherapy for their disease; subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
- Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- The patient must be recovered from a prior major surgery; the major surgery must be performed at least 4 weeks prior to consent date
- Platelets >= 125 x 10^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab] and expansion cohorts for all arms, platelets >= 100 x 10^9/L)
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- Hemoglobin >= 10 g/dL (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab] and expansion cohorts for all arms, hemoglobin >= 9 g/dL)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (For Arm L pembrolizumab, Arm M nivolumab and Arms N, O, P [nivolumab and ipilimumab], ANC >= 1.0 x 10^9/L)
- Transfusions and growth factors are allowed
- Alanine transaminase (alanine aminotransferase [ALT]) =< 2 x upper normal limit (ULN) (in the expansion cohort, patients with known liver involvement may have ALT =< 5 x ULN); aspartate aminotransferase (AST) =< 2 x ULN (in the expansion cohort, patients with known liver involvement may have AST =< 5 x ULN)
- Alkaline phosphatase < 4 x ULN
- Total bilirubin =< 2 x ULN (in the expansion cohort, patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of =< 3 x ULN)
- Renal function defined as a calculated or measured glomerular filtration rate (GFR) >= 30 mL/min. For patients with renal cell carcinoma (RCC), the GFR may be defined as >= 25 mL/min
- The patient has recovered to grade =< 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia; the exceptions for such effects are allowed lab values of =< grade 2 specified elsewhere in these inclusion criteria
- Life expectancy of at least 12 weeks
- Able to swallow and retain oral medication
- Patients must give informed consent according to the rules and regulations of the individual participating sites
- Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during/after 3 months post dose; a woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant; this includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices
- For the Arm B (paclitaxel) expansion cohort, patients must have ovarian carcinoma, fallopian tube, or peritonea carcinoma
- For Arm C (eribulin) expansion cohort, patients must have triple negative breast cancer (eribulin naive)
- For Arm M (nivolumab) expansion phase, patients must have biopsiable disease
- For the Arm N (nivolumab and ipilimumab), patients must have metastatic or unresectable renal cell carcinoma (RCC)
- For the Arm O (nivolumab and ipilimumab) escalation and expansion Cohort O-1, patients must have metastatic or unresectable melanoma
- For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must have metastatic or advanced solid tumors (non-melanoma, non-renal cell carcinoma, or non- non-small cell lung carcinoma)
- For the Arm P (nivolumab and ipilimumab), patients must have metastatic or unresectable non-small cell lung carcinoma (NSCLC)
Who cannot join
- Evidence of complete or partial bowel obstruction
- Patients with primary central nervous system (CNS) tumor or CNS tumor involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is:
- > 4 weeks from prior therapy completion (including radiation and/or surgery)
- Clinically stable with respect to the CNS tumor at the time of study entry
- Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement
- Not receiving anti-convulsive medications (that were started for brain metastases)
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- Need of total parenteral nutrition
- Prior treatment with an agent targeting the exportin
- Allergic to selinexor or any of the chemotherapy intended to receive
- Pregnancy or lactation
- Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) =< 3 weeks prior to study drug administration date
- Chemotherapy, or immunotherapy or any other systemic anticancer therapy =< 3 weeks prior to study drug administration date; patients receiving anti-PD-1 treatment, and continue to receiving this treatment in combination with selinexor (Arms L, M, N, O, and P), can start receiving the selinexor and anti-PD-1 combination without washout of the prior anti-PD-1 antibody
- Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated)
- Major surgery within four weeks before consent date
- Unstable cardiovascular function: symptomatic ischemia (chest pain of cardiac origin), or uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] will not be excluded), or congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or myocardial infarction (MI) within 3 months of consent date
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose; active infection with concurrent treatment is acceptable only if the patient is clinically stable
- Significantly diseased (as determined by the principal investigator [PI] or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea
- Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date
- Concurrent therapy with approved or investigational anticancer therapeutics
- Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception; highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 3 months after the end of study treatment; women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months)
- For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects with an active, known or suspected autoimmune disease; subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), subjects receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or other form of immunosuppressive therapy within 7 days before the first dose of study treatment; use of inhaled or topical steroids or systemic corticosteroids =< 10 mg is permitted; in addition, physiologic steroid replacement with hydrocortisone is allowed
- For Arms L (pembrolizumab) and M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab), history of a prior grade 3 or 4 immune-related adverse event (irAE) or any grade ocular irAE from prior immunotherapy
- For the Arm O (nivolumab and ipilimumab) expansion Cohort O-2, patients must not have melanoma, RCC, or NSCLC
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
MD Anderson in The Woodlands
Conroe, Texas, 77384
M D Anderson Cancer Center
Houston, Texas, 77030
MD Anderson West Houston
Houston, Texas, 77079
MD Anderson League City
League City, Texas, 77573
MD Anderson in Sugar Land
Sugar Land, Texas, 77478
About this study
This phase Ib trial studies the side effects and best dose of selinexor when given together with several different standard chemotherapy or immunotherapy regimens in treating patients with malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Selinexor may stop the growth of cancer cells by blocking enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Studying selinexor with different standard chemotherapy or immunotherapy regimens may help doctors learn the side effects and best dose of selinexor that can be given with different types of treatments in one study.
Read the detailed description
PRIMARY OBJECTIVE:
- To establish the safety and tolerability of selinexor when given in combination with standard chemotherapy or immunotherapy regimens.
SECONDARY OBJECTIVE:
- To determine disease control rate, objective tumor response rate, and progression free survival of selinexor administered with standard chemotherapy or immunotherapy treatments.
EXPLORATORY OBJECTIVES:
- To determine the correlation of translational biomarkers. II. To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy.
III. To assess the efficacy of olanzapine as incorporated in the National Comprehensive Cancer Network (NCCN) guidelines for the management of chemotherapy-induced nausea and cachexia.
OUTLINE: This is a dose-escalation study of selinexor. Patients are assigned to 1 of 15 treatment arms.
ARM A: Patients receive selinexor orally (PO) on days 1, 8, and 15 and carboplatin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM B: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles, of combination treatment, patients can continue single agent selinexor until disease progression.
ARM C: Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
ARM D: Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM E: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending on cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM F: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM G: Patients receive selinexor PO on days 1, 8, and 15 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM H: Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil continuous IV and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM I: Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM J: Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM K: Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (ARM CLOSED)
ARM L: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM M: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARMS N AND O: Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM P: Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients may continue to receive selinexor and chemotherapy after confirmed progressive disease in the absence of clinical deterioration and if the investigator considers that the patient continues to receive benefit from the treatment.
After completion of study treatment, patients are followed up every 12 weeks for 1 year.
- Conditions
- Advanced Malignant Solid Neoplasm, Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Fallopian Tube Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Solid Neoplasm
- Being tested
- Capecitabine, Carboplatin, Cyclophosphamide, Doxorubicin, Eribulin
- Medical subject headings
- Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Melanoma, Carcinoma, Renal Cell, Ovarian Neoplasms, Lung Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Ro 09-1978/000, Xeloda
Given PO
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
DoxorubicinDrug
Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Given IV
EribulinDrug
Also called ER-086526
Given IV
FluorouracilDrug
Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Given IV
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010
Given IV
Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11
Given IV
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given IV
NivolumabBiological
Also called BMS-936558, CMAB819, MDX-1106, NIVO
Given IV
OlaparibDrug
Also called AZD 2281, AZD-2281, AZD2281, KU-0059436
Given PO
OxaliplatinDrug
Also called 1-OHP, Ai Heng, Aiheng, Dacotin
Given IV
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
PemetrexedDrug
Also called MTA, Multitargeted Antifolate, Pemfexy
Given IV
SelinexorDrug
Also called ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330
Given PO
TopotecanDrug
Also called Hycamptamine, Topotecan Lactone
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm A (selinexor, carboplatin) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Carboplatin; Drug: Selinexor |
| Arm B (selinexor, paclitaxel) | Experimental | Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles of combination treatment, patients can continue single agent selinexor until disease progression. Receives: Drug: Paclitaxel; Drug: Selinexor |
| Arm C (selinexor, eribulin) | Experimental | Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Eribulin; Drug: Selinexor |
| Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Selinexor |
| Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending con cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Selinexor |
| Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Carboplatin; Drug: Pemetrexed; Drug: Selinexor |
| Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, and 15 and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Selinexor; Drug: Topotecan |
| Arm H (selinexor, FOLFIRI) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV continuously over 48 hours and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Drug: Leucovorin Calcium; Drug: Selinexor |
| Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Irinotecan Hydrochloride; Drug: Selinexor |
| Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. Receives: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Selinexor |
| Arm K (selinexor, olaparib) (ARM CLOSED) | Experimental | Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Olaparib; Drug: Selinexor |
| Arm L (selinexor, pembrolizumab) | Experimental | Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Pembrolizumab; Drug: Selinexor |
| Arm M (selinexor, nivolumab | Experimental | Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Nivolumab; Drug: Selinexor |
| Arm P (selinexor, nivolumab, ipilimumab) | Experimental | Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Receives: Biological: Ipilimumab; Biological: Nivolumab; Drug: Selinexor |
| Arms N and O (selinexor, nivolumab, ipilimumab) | Experimental | Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Receives: Biological: Ipilimumab; Biological: Nivolumab; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measured: Up to 3 years
Secondary outcomes (5)
Disease control rate (complete response, partial response + stable disease for at least 6 months
Assessed according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). Estimated separately for each cohort with appropriate 95% confidence intervals.
Measured: Up to 3 years
Objective tumor response rate (complete response + partial response)
Assessed according to RECIST 1.1 criteria. Estimated separately for each cohort with appropriate 95% confidence intervals.
Measured: Up to 3 years
Progression-free survival (PFS)
PFS distribution will be estimated using the Kaplan-Meier product limit method and summary measures such as the median value and probabilities will be reported at selected times (with appropriate 95% confidence intervals).
Measured: The time between the course 1 start date and the date of disease progression or death, whichever is reported first, assessed up to 3 years
Overall survival (OS)
OS distribution will be estimated using the Kaplan-Meier product limit method and summary measures such as the median value and probabilities will be reported at selected times (with appropriate 95% confidence intervals).
Measured: Up to 3 years
Incidence of adverse events
Will be graded according to NCI CTCAE version 4.03.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study start26 Jun 2015
- Primary completion16 Sep 2024
- Study completion16 Sep 2024
Why it stopped: Administratively Complete
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Aung Naing, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02419495
- Sponsor's protocol ID
- 2014-0640
- Other IDs
- NCI-2015-00693, 2014-0640
- Status last verified
- Sep 2024
- First submitted
- 14 Apr 2015
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Alhalabi O, Gouda MA, Milton DR, Momin HA, Yilmaz B, Stephen B, Ejezie CL, Moyers JT, Gurses SA, How J, Fu S, Rodon J, Hong DS, Piha-Paul SA, Subbiah V, Elena Dumbrava E, Karp DD, Janku F, Meric-Bernstam F, Tannir NM, Naing A. A Phase IB Trial of Selinexor in Combination With Immune Checkpoint Blockade in Patients With Advanced Renal Cell Carcinoma. Cancer Med. 2025 Feb;14(4):e70280. doi: 10.1002/cam4.70280.
PubMed 39945382Gouda MA, Zarifa A, Yang Y, Stephen B, Gurses SA, Sprenger A, Tian Y, Derbala MH, Oliva IG, Meric-Bernstam F, Patel SP. Selinexor (KPT-330) in Combination with Immune Checkpoint Inhibition in Uveal Melanoma: A Phase 1B Trial. J Immunother Precis Oncol. 2025 Jan 15;8(1):82-88. doi: 10.36401/JIPO-24-10. eCollection 2025 Feb.
PubMed 39816915Altan M, Tu J, Milton DR, Yilmaz B, Tian Y, Fossella FV, Mott FE, Blumenschein GR, Stephen B, Karp DD, Meric-Bernstam F, Heymach JV, Naing A. Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non-small cell lung cancer. Cancer. 2023 Sep 1;129(17):2685-2693. doi: 10.1002/cncr.34820. Epub 2023 May 2.
PubMed 37129197Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Fu S, Subbiah V, Hong DS, Yap TA, Shah J, Milton DR, McQuinn L, Gong J, Tran Y, Carter BW, Colen R, Meric-Bernstam F, Naing A. Selinexor in combination with standard chemotherapy in patients with advanced or metastatic solid tumors. Exp Hematol Oncol. 2021 Dec 29;10(1):59. doi: 10.1186/s40164-021-00251-0.
PubMed 34965890Thein KZ, Karp DD, Tsimberidou A, Gong J, Sulovic S, Shah J, Milton DR, Hong DS, Janku F, McQuinn L, Stephen BA, Colen R, Carter BW, Yap TA, Piha-Paul SA, Fu S, Meric-Bernstam F, Naing A. Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. Invest New Drugs. 2022 Apr;40(2):290-299. doi: 10.1007/s10637-021-01188-1. Epub 2021 Sep 25.
PubMed 34562230Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Zarifa A, Shah J, Milton DR, Bean S, McQuinn L, Gong J, Colen R, Carter BW, Subbiah V, Ogbonna DC, Pant S, Meric-Bernstam F, Naing A. Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study. Invest New Drugs. 2021 Oct;39(5):1357-1365. doi: 10.1007/s10637-021-01119-0. Epub 2021 Apr 28.
PubMed 33909232
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02419495
- Acronym / sponsor ID
- 2014-0640
- Conditions
- Advanced Malignant Solid Neoplasm, Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Fallopian Tube Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administratively Complete
- Enrolment
- 221 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 Jun 2015 (actual)
- Primary completion
- 16 Sep 2024 (actual)
- Study completion
- 16 Sep 2024 (actual)
- First posted
- 17 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib trial studies the side effects and best dose of selinexor when given together with several different standard chemotherapy or immunotherapy regimens in treating patients with malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Selinexor may stop the growth of cancer cells by blocking enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Studying selinexor with different standard chemotherapy or immunotherapy regimens may help doctors learn the side effects and best dose of selinexor that can be given with different types of treatments in one study.
Detailed description
PRIMARY OBJECTIVE:
- To establish the safety and tolerability of selinexor when given in combination with standard chemotherapy or immunotherapy regimens.
SECONDARY OBJECTIVE:
- To determine disease control rate, objective tumor response rate, and progression free survival of selinexor administered with standard chemotherapy or immunotherapy treatments.
EXPLORATORY OBJECTIVES:
- To determine the correlation of translational biomarkers. II. To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy.
III. To assess the efficacy of olanzapine as incorporated in the National Comprehensive Cancer Network (NCCN) guidelines for the management of chemotherapy-induced nausea and cachexia.
OUTLINE: This is a dose-escalation study of selinexor. Patients are assigned to 1 of 15 treatment arms.
ARM A: Patients receive selinexor orally (PO) on days 1, 8, and 15 and carboplatin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM B: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles, of combination treatment, patients can continue single agent selinexor until disease progression.
ARM C: Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.
ARM D: Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM E: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending on cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM F: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM G: Patients receive selinexor PO on days 1, 8, and 15 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM H: Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil continuous IV and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM I: Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM J: Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)
ARM K: Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (ARM CLOSED)
ARM L: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM M: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARMS N AND O: Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM P: Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients may continue to receive selinexor and chemotherapy after confirmed progressive disease in the absence of clinical deterioration and if the investigator considers that the patient continues to receive benefit from the treatment.
After completion of study treatment, patients are followed up every 12 weeks for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Arm A (selinexor, carboplatin) (ARM CLOSED) | Experimental | Drug: Carboplatin, Drug: SelinexorPatients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. |
| Arm B (selinexor, paclitaxel) | Experimental | Drug: Paclitaxel, Drug: SelinexorPatients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles of combination treatment, patients can continue single agent selinexor until disease progression. |
| Arm C (selinexor, eribulin) | Experimental | Drug: Eribulin, Drug: SelinexorPatients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. |
| Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED) | Experimental | Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: SelinexorPatients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. |
| Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED) | Experimental | Drug: Carboplatin, Drug: Paclitaxel, Drug: SelinexorPatients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending con cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. |
| Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED) | Experimental | Drug: Carboplatin, Drug: Pemetrexed, Drug: SelinexorPatients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. |
| Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED) | Experimental | Drug: Selinexor, Drug: TopotecanPatients receive selinexor PO on days 1, 8, and 15 and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. |
| Arm H (selinexor, FOLFIRI) (ARM CLOSED) | Experimental | Drug: Fluorouracil, Drug: Irinotecan Hydrochloride, Drug: Leucovorin Calcium, Drug: SelinexorPatients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV continuously over 48 hours and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. |
| Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED) | Experimental | Drug: Irinotecan Hydrochloride, Drug: SelinexorPatients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. |
| Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED) | Experimental | Drug: Capecitabine, Drug: Oxaliplatin, Drug: SelinexorPatients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. |
| Arm K (selinexor, olaparib) (ARM CLOSED) | Experimental | Drug: Olaparib, Drug: SelinexorPatients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm L (selinexor, pembrolizumab) | Experimental | Biological: Pembrolizumab, Drug: SelinexorPatients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| Arm M (selinexor, nivolumab | Experimental | Biological: Nivolumab, Drug: SelinexorPatients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm P (selinexor, nivolumab, ipilimumab) | Experimental | Biological: Ipilimumab, Biological: Nivolumab, Drug: SelinexorPatients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. |
| Arms N and O (selinexor, nivolumab, ipilimumab) | Experimental | Biological: Ipilimumab, Biological: Nivolumab, Drug: SelinexorPatients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment; patients in Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) that have Food and Drug Administration (FDA)-approved indications for nivolumab, ipilimumab, and pembrolizumab do not have to fail first line nivolumab, ipilimumab, or pembrolizumab, and these patients may be treatment naïve if they have disease where pembrolizumab or nivolumab are FDA approved for the first-line setting
- For all arms except Arm L (pembrolizumab), Arm M (nivolumab), and Arms N, O, P (nivolumab and ipilimumab) patients must have failed prior standard curative chemotherapy for their disease; subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
- Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- The patient must be recovered from a prior major surgery; the major surgery must be performed at least 4 weeks prior to consent date
Key exclusion criteria (25 listed)
- Evidence of complete or partial bowel obstruction
- Patients with primary central nervous system (CNS) tumor or CNS tumor involvement; however, patients with metastatic CNS tumors may participate in this study if the patient is:
- Need of total parenteral nutrition
- Prior treatment with an agent targeting the exportin
- Allergic to selinexor or any of the chemotherapy intended to receive
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineAlso: Ro 09-1978/000, XelodaGiven PO | Drug | Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED) |
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Arm A (selinexor, carboplatin) (ARM CLOSED), Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED), Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED) |
| DoxorubicinAlso: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, HydroxyldaunorubicinGiven IV | Drug | Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED) |
| EribulinAlso: ER-086526Given IV | Drug | Arm C (selinexor, eribulin) |
| FluorouracilAlso: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedioneGiven IV | Drug | Arm H (selinexor, FOLFIRI) (ARM CLOSED) |
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010Given IV | Biological | Arm P (selinexor, nivolumab, ipilimumab), Arms N and O (selinexor, nivolumab, ipilimumab) |
| Irinotecan HydrochlorideAlso: Campto, Camptosar, Camptothecin 11, Camptothecin-11Given IV | Drug | Arm H (selinexor, FOLFIRI) (ARM CLOSED), Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED) |
| Leucovorin CalciumAlso: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium FolinateGiven IV | Drug | Arm H (selinexor, FOLFIRI) (ARM CLOSED) |
| NivolumabAlso: BMS-936558, CMAB819, MDX-1106, NIVOGiven IV | Biological | Arm M (selinexor, nivolumab, Arm P (selinexor, nivolumab, ipilimumab), Arms N and O (selinexor, nivolumab, ipilimumab) |
| OlaparibAlso: AZD 2281, AZD-2281, AZD2281, KU-0059436Given PO | Drug | Arm K (selinexor, olaparib) (ARM CLOSED) |
| OxaliplatinAlso: 1-OHP, Ai Heng, Aiheng, DacotinGiven IV | Drug | Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED) |
| PaclitaxelAlso: Anzatax, Asotax, Bristaxol, PraxelGiven IV | Drug | Arm B (selinexor, paclitaxel), Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Arm L (selinexor, pembrolizumab) |
| PemetrexedAlso: MTA, Multitargeted Antifolate, PemfexyGiven IV | Drug | Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED) |
| SelinexorAlso: ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330Given PO | Drug | Arm A (selinexor, carboplatin) (ARM CLOSED), Arm B (selinexor, paclitaxel), Arm C (selinexor, eribulin), Arm D (selinexor, doxorubicin, cyclophosphamide) (ARM CLOSED), Arm E (selinexor, carboplatin, paclitaxel) (ARM CLOSED), Arm F (selinexor, carboplatin, pemetrexed) (ARM CLOSED), Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED), Arm H (selinexor, FOLFIRI) (ARM CLOSED), Arm I (selinexor, irinotecan hydrochloride) (ARM CLOSED), Arm J (selinexor, capecitabine, oxaliplatin) (ARM CLOSED), Arm K (selinexor, olaparib) (ARM CLOSED), Arm L (selinexor, pembrolizumab), Arm M (selinexor, nivolumab, Arm P (selinexor, nivolumab, ipilimumab), Arms N and O (selinexor, nivolumab, ipilimumab) |
| TopotecanAlso: Hycamptamine, Topotecan LactoneGiven IV | Drug | Arm G (selinexor, topotecan hydrochloride) (ARM CLOSED) |
Primary outcome
Incidence of adverse events
Time frame: Up to 3 years
Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
5 secondary outcomes
Disease control rate (complete response, partial response + stable disease for at least 6 months
Time frame: Up to 3 years
Objective tumor response rate (complete response + partial response)
Time frame: Up to 3 years
Progression-free survival (PFS)
Time frame: The time between the course 1 start date and the date of disease progression or death, whichever is reported first, assessed up to 3 years
Overall survival (OS)
Time frame: Up to 3 years
Incidence of adverse events
Time frame: Up to 3 years
Results and safety
The study was stopped early (reason given: Administratively Complete). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Derived from this study: PubMed 39945382Alhalabi O, Gouda MA, Milton DR, Momin HA, Yilmaz B, Stephen B, Ejezie CL, Moyers JT, Gurses SA, How J, Fu S, Rodon J, Hong DS, Piha-Paul SA, Subbiah V, Elena Dumbrava E, Karp DD, Janku F, Meric-Bernstam F, Tannir NM, Naing A. A Phase IB Trial of Selinexor in Combination With Immune Checkpoint Blockade in Patients With Advanced Renal Cell Carcinoma. Cancer Med. 2025 Feb;14(4):e70280. doi: 10.1002/cam4.70280.
- Derived from this study: PubMed 39816915Gouda MA, Zarifa A, Yang Y, Stephen B, Gurses SA, Sprenger A, Tian Y, Derbala MH, Oliva IG, Meric-Bernstam F, Patel SP. Selinexor (KPT-330) in Combination with Immune Checkpoint Inhibition in Uveal Melanoma: A Phase 1B Trial. J Immunother Precis Oncol. 2025 Jan 15;8(1):82-88. doi: 10.36401/JIPO-24-10. eCollection 2025 Feb.
- Derived from this study: PubMed 37129197Altan M, Tu J, Milton DR, Yilmaz B, Tian Y, Fossella FV, Mott FE, Blumenschein GR, Stephen B, Karp DD, Meric-Bernstam F, Heymach JV, Naing A. Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non-small cell lung cancer. Cancer. 2023 Sep 1;129(17):2685-2693. doi: 10.1002/cncr.34820. Epub 2023 May 2.
- Derived from this study: PubMed 34965890Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Fu S, Subbiah V, Hong DS, Yap TA, Shah J, Milton DR, McQuinn L, Gong J, Tran Y, Carter BW, Colen R, Meric-Bernstam F, Naing A. Selinexor in combination with standard chemotherapy in patients with advanced or metastatic solid tumors. Exp Hematol Oncol. 2021 Dec 29;10(1):59. doi: 10.1186/s40164-021-00251-0.
- Derived from this study: PubMed 34562230Thein KZ, Karp DD, Tsimberidou A, Gong J, Sulovic S, Shah J, Milton DR, Hong DS, Janku F, McQuinn L, Stephen BA, Colen R, Carter BW, Yap TA, Piha-Paul SA, Fu S, Meric-Bernstam F, Naing A. Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study. Invest New Drugs. 2022 Apr;40(2):290-299. doi: 10.1007/s10637-021-01188-1. Epub 2021 Sep 25.
- Derived from this study: PubMed 33909232Thein KZ, Piha-Paul SA, Tsimberidou A, Karp DD, Janku F, Zarifa A, Shah J, Milton DR, Bean S, McQuinn L, Gong J, Colen R, Carter BW, Subbiah V, Ogbonna DC, Pant S, Meric-Bernstam F, Naing A. Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study. Invest New Drugs. 2021 Oct;39(5):1357-1365. doi: 10.1007/s10637-021-01119-0. Epub 2021 Apr 28.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aung Naing, MD principal investigator
M.D. Anderson Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Capecitabine, Carboplatin and Cyclophosphamide in people with Advanced Malignant Solid Neoplasm and Clinical Stage III Cutaneous Melanoma AJCC v8, run by M.D. Anderson Cancer Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Administratively Complete). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02419495, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025; AzTrials last refreshed its copy on 7 Nov 2026.