Solid TumorPhase 1NCT01607905
Safety Study of KPT-330 (Selinexor) in Patients With Advanced or Metastatic Solid Tumor Cancer
A Phase 1 study testing Selinexor and Acetaminophen in people with Solid Tumor, run by Karyopharm Therapeutics Inc at 6 sites in 3 countries.
Trial summary
Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- Selinexor and Acetaminophen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 18 Jun 2012to 15 Mar 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis.
- Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:
- Up to 12 patients with metastatic colorectal cancer with a history of progression or recurrence following prior fluoropyrimidine, irinotecan and platinum containing regimens as well as bevacizumab. In addition, patients with Kras wild type tumor must have received at least one EGFR blocker.
- Up to 6 patients with histological or cytological documentation of advanced ovarian, fallopian tube, or primary peritoneal carcinoma with a history of progression or recurrence following at least one prior platinum and one taxane based chemotherapy
- Up to 12 patients with incurable Squamous cell cancers as follows:
- A minimum of 4 Squamous Non-Small Cell Lung Cancer (Sq-NSCLC)
Show all 13Show fewer
- A minimum of 4 Squamous Cell Carcinomas of the Head and Neck (Sq-HNC)
- Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell Carcinomas should have a documented history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen
- Up to 6 patients with castration-resistant prostate cancer (CRPC) that was pathologically confirmed as adenocarcinoma of the prostate and with evidence of metastatic disease on bone scan or other imaging. Patient must have progressive disease after at least one hormonal treatment and one cytotoxic therapy e.g. with docetaxel, mitoxantrone.
- Up to 12 patients with unresectable metastatic melanoma whose disease progressed on at least 1 prior systemic anticancer regimen (chemotherapy, biological or immunotherapy, or targeted therapy). Enrollment to this cohort may have been stopped before reaching 12 patients once the dose-escalation portion of the study was completed.
- Approximately 6 patients with advanced or metastatic solid tumors were to be enrolled on Schedule 8 at a starting dose of 35 mg/m^2 to assess general tolerability and activity of selinexor.
- Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.
- Both Dose Escalation and Expansion Phases: There is no upper limit on the number of prior treatments provided that all inclusion criteria are met and exclusion criteria are not met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimes.
Who cannot join
- Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1;
- Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States4 sites
Gabrail Cancer Center
Canton, Ohio, 44718
Karmanos Cancer Institute
Detroit, Michigan, 48201
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Advanced or Metastatic Solid Tumor Malignancies
Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies.
Read the detailed description
This is a phase 1a and phase 1b, open-label, dose-escalation study to evaluate the safety and tolerability of selinexor and determine the RP2D in patients with solid tumor malignancies.
- Conditions
- Solid Tumor
- Being tested
- Selinexor, Acetaminophen
- Keywords
- Selinexor, KPT-330, Squamous Cell Carcinoma, Glioblastoma multiforme, Adenocarcinoma, Melanoma, Colorectal cancer, Gynecological cancer, Castrate-resistant Prostate Cancer, Other solid tumors
- Medical subject headings
- Carcinoma, Squamous Cell, Glioblastoma, Adenocarcinoma, Melanoma, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called KPT-330, XPOVIO
Participants in this study will receive selinexor orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m^2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in 4-week (28 days for schedule 1 to 7) and 3-week (21 days for schedule 8) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.
AcetaminophenDrug
Oral 500 mg (in Cycle 1, Week 1) to 1000 mg (in Cycle 1, Week 2 and onwards) of acetaminophen will be administered 1 hour prior to each selinexor dose up to 8 doses per cycle (28 days per cycle)
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Colorectal Cancer) | Experimental | Participants with colorectal cancer and liver metastasis received oral selinexor as single agent in 8 schedules, Schedule1: ≤12milligrams per meter square(mg/m^2) 3 times weekly(TIW) during Weeks 1 and 3, twice weekly(BIW) during Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule2: >12mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule3: ≥30mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle(28 days/cycle); Schedule4: ≥20mg/m^2 BIW(Days 1 and 2) up to 8 doses/cycle(28 days/cycle); Schedule5: ≥35mg/m^2 BIW(Days 1 and 4) up to 8 doses(28 days/cycle); Schedule6: ≥20mg/m^2 BIW(Days 1 and 4) after 500 mg(Week 1) to 1000 mg(Week 2 onwards) acetaminophen(given 1 hour prior to each selinexor dose) up to 8 doses/cycle (28 days/cycle); Schedule7: ≥50mg/m^2 once weekly(QW) up to 4 doses/cycle(28 days per cycle); Schedule8: ≥45mg/m^2 BIW(Days 1 and 3) up to 4 doses/cycle(21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor; Drug: Acetaminophen |
| Arm B (Gynecological Cancer) | Experimental | Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor |
| Arm C (Squamous Cell Cancer) | Experimental | Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor |
| Arm D (Castrate-resistant Prostate Cancer) | Experimental | Participants with castrate-resistant prostate cancer (CRPC) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor |
| Arm E (Glioblastoma Multiforme) | Experimental | Participants with glioblastoma multiforme (GBM) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor |
| Arm F (Melanoma) | Experimental | Participants with Melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor |
| Arm G (Other Solid Tumors) | Experimental | Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. Receives: Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria; is fatal, life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. Number of participants with TEAEs and TESAEs were reported.
Measured: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
Number of Participants With Treatment-related Treatment-emergent Adverse Events
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A treatment-related AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product; the event had a causal relationship with the treatment or usage.
Measured: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Greater Than or Equal to Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.
Measured: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
Number of Participants Who Experienced Dose Limiting Toxicity (DLT)
Evaluation of DLTs was only conducted in participants who participated in the Dose-escalation Phase. A DLT was defined as any of the following, considered possibly related to drug administration, occurring in the first 28 days (or 21 days for participants on Schedule 8) at the target dose (ie, for Schedule 2 this meant the first 4 weeks after the 12 mg/m2 run-in week): Missed selinexor doses due to drug-related toxicities, discontinuation of a participant due to a toxicity that was at least possibly related to study drug before completing Cycle 1.
Measured: Cycle 1 only (28-day cycle)
Recommended Phase 2 Dose (RP2D)
The RP2D was the maximum tolerated dose (MTD) or less. MTD was defined as the next lower dose level below the one in which >1 of 3 participants or ≥2 of 6 participants experienced DLT, provided that dose level was ≤25 percent (%) lower than the highest (intolerable) dose tested. If the projected MTD was >25% lower than the highest dose tested, then an additional cohort of ≥3 participants was added at a dose that was intermediate between the intolerable dose and the next lower dose.
Measured: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
Secondary outcomes (12)
Maximum Observed Plasma Concentration (Cmax) of Selinexor
Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Time of Maximum Observed Concentration in Plasma (Tmax) of Selinexor
Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Area Under the Concentration Time Curve From the Time of Dosing to Time in Plasma (AUC0-t) of Selinexor
AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Area Under the Concentration Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Selinexor
AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated). It was calculated as AUC0-t + Ct/kel, where: Ct = the last observed non-zero concentration and Kel = elimination rate constant.
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Elimination Half-Life (t1/2) of Selinexor
t1/2 was defined as elimination half-life, it was calculated as ln(2)/kel, where In = natural logarithm and kel = elimination rate constant.
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Apparent Total Body Clearance (CL/F) of Selinexor
CL/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram).
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Apparent Volume of Distribution of Selinexor (Vd/F)
Vd/F was calculated as Dose/(kel * AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram).
Measured: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Number of Participants With Best Overall Response (BOR)
BOR is response recorded from start of treatment until disease progression/recurrence. Best lesion response was defined by Recist Criteria V1 (for target and non-target lesions) and RANO criteria (for glioblastoma multiforme): complete response (CR)- disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to less than (<) 10 mm; partial response (PR)- at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum longest diameter; stable disease (SD)- steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; progressive disease (PD): at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded since treatment started. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm, or appearance of one or more new lesions.
Measured: Up to maximum duration of 45 months
Percentage of Participants With Objective Response
Objective response rate (ORR) was determined as percentage of participants who had either CR or PR, as defined by RECIST v1.1 (for solid tumors). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to <10 mm and PR was defined as at least 30% decrease in sum of diameters of target lesions. ORR was calculated as a proportion and included a 2 sided 95% CI using the exact (Clopper-Pearson) method.
Measured: Up to maximum duration of 45 months
Duration of Stable Disease (SD)
Duration of stable disease was defined as the time from the date of first dose to first documented radiologic evidence of disease recurrence or progression, as defined by RECIST v1.1 (for solid tumors) or RANO criteria (for GBM and AnaA).
Measured: From first dose of study drug administration to first documented evidence of disease recurrence or progression (maximum duration of 45 months)
Progression-free Survival (PFS)
Progression-free survival was calculated from the date of first dose of study treatment to first documented evidence of disease recurrence or progression or death due to any cause. Patients who are last known to be alive and without evidence of progression will be censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, patients are censored at the time of last evaluable disease assessment prior to the missed assessment. Progressive disease was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease.
Measured: From start of study drug administration until PD or discontinuation from the study or death (maximum duration of 45 months)
Overall Survival (OS)
OS was calculated from the date of first dose to date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, were censored at the day they were last known to be alive. The OS was calculated using the Kaplan-Meier method.
Measured: From first dose of study drug administration to date of death (maximum duration of 45 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2012 (estimated)
- Study start18 Jun 2012
- Primary completion15 Mar 2016
- Study completion15 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- 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
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01607905
- Sponsor's protocol ID
- KCP-330-002
- Status last verified
- Jan 2023
- First submitted
- 16 May 2012
- Last updated
- 26 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Machlus KR, Wu SK, Vijey P, Soussou TS, Liu ZJ, Shacham E, Unger TJ, Kashyap T, Klebanov B, Sola-Visner M, Crochiere M, Italiano JE Jr, Landesman Y. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood. 2017 Aug 31;130(9):1132-1143. doi: 10.1182/blood-2016-11-752840. Epub 2017 Jun 19.
PubMed 28630120
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Advanced or Metastatic Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT01607905
- Acronym / sponsor ID
- KCP-330-002
- Conditions
- Solid Tumor
- Keywords
- Selinexor, KPT-330, Squamous Cell Carcinoma, Glioblastoma multiforme, Adenocarcinoma, Melanoma, Colorectal cancer, Gynecological cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Karyopharm Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- 18 Jun 2012 (actual)
- Primary completion
- 15 Mar 2016 (actual)
- Study completion
- 15 Mar 2016 (actual)
- First posted
- 30 May 2012 (estimated)
- Results
- Posted 30 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies.
Detailed description
This is a phase 1a and phase 1b, open-label, dose-escalation study to evaluate the safety and tolerability of selinexor and determine the RP2D in patients with solid tumor malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Arm A (Colorectal Cancer) | Experimental | Drug: Selinexor, Drug: AcetaminophenParticipants with colorectal cancer and liver metastasis received oral selinexor as single agent in 8 schedules, Schedule1: ≤12milligrams per meter square(mg/m^2) 3 times weekly(TIW) during Weeks 1 and 3, twice weekly(BIW) during Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule2: >12mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule3: ≥30mg/m^2 BIW(Days 1 and 3) up to 8 doses/cycle(28 days/cycle); Schedule4: ≥20mg/m^2 BIW(Days 1 and 2) up to 8 doses/cycle(28 days/cycle); Schedule5: ≥35mg/m^2 BIW(Days 1 and 4) up to 8 doses(28 days/cycle); Schedule6: ≥20mg/m^2 BIW(Days 1 and 4) after 500 mg(Week 1) to 1000 mg(Week 2 onwards) acetaminophen(given 1 hour prior to each selinexor dose) up to 8 doses/cycle (28 days/cycle); Schedule7: ≥50mg/m^2 once weekly(QW) up to 4 doses/cycle(28 days per cycle); Schedule8: ≥45mg/m^2 BIW(Days 1 and 3) up to 4 doses/cycle(21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Arm B (Gynecological Cancer) | Experimental | Drug: SelinexorParticipants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Arm C (Squamous Cell Cancer) | Experimental | Drug: SelinexorParticipants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Arm D (Castrate-resistant Prostate Cancer) | Experimental | Drug: SelinexorParticipants with castrate-resistant prostate cancer (CRPC) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Arm E (Glioblastoma Multiforme) | Experimental | Drug: SelinexorParticipants with glioblastoma multiforme (GBM) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Arm F (Melanoma) | Experimental | Drug: SelinexorParticipants with Melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity. |
| Arm G (Other Solid Tumors) | Experimental | Drug: SelinexorParticipants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: >12 mg/m^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, 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 (13 listed)
- Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis.
- Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:
- Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.
- Both Dose Escalation and Expansion Phases: There is no upper limit on the number of prior treatments provided that all inclusion criteria are met and exclusion criteria are not met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimes.
Key exclusion criteria (2 listed)
- Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1;
- Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
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 |
|---|---|---|
| SelinexorAlso: KPT-330, XPOVIOParticipants in this study will receive selinexor orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m^2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in 4-week (28 days for schedule 1 to 7) and 3-week (21 days for schedule 8) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted. | Drug | Arm A (Colorectal Cancer), Arm B (Gynecological Cancer), Arm C (Squamous Cell Cancer), Arm D (Castrate-resistant Prostate Cancer), Arm E (Glioblastoma Multiforme), Arm F (Melanoma), Arm G (Other Solid Tumors) |
| AcetaminophenOral 500 mg (in Cycle 1, Week 1) to 1000 mg (in Cycle 1, Week 2 and onwards) of acetaminophen will be administered 1 hour prior to each selinexor dose up to 8 doses per cycle (28 days per cycle) | Drug | Arm A (Colorectal Cancer) |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria; is fatal, life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. Number of participants with TEAEs and TESAEs were reported.
Number of Participants With Treatment-related Treatment-emergent Adverse Events
Time frame: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A treatment-related AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product; the event had a causal relationship with the treatment or usage.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Greater Than or Equal to Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Time frame: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.
Number of Participants Who Experienced Dose Limiting Toxicity (DLT)
Time frame: Cycle 1 only (28-day cycle)
Evaluation of DLTs was only conducted in participants who participated in the Dose-escalation Phase. A DLT was defined as any of the following, considered possibly related to drug administration, occurring in the first 28 days (or 21 days for participants on Schedule 8) at the target dose (ie, for Schedule 2 this meant the first 4 weeks after the 12 mg/m2 run-in week): Missed selinexor doses due to drug-related toxicities, discontinuation of a participant due to a toxicity that was at least possibly related to study drug before completing Cycle 1.
Recommended Phase 2 Dose (RP2D)
Time frame: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)
The RP2D was the maximum tolerated dose (MTD) or less. MTD was defined as the next lower dose level below the one in which >1 of 3 participants or ≥2 of 6 participants experienced DLT, provided that dose level was ≤25 percent (%) lower than the highest (intolerable) dose tested. If the projected MTD was >25% lower than the highest dose tested, then an additional cohort of ≥3 participants was added at a dose that was intermediate between the intolerable dose and the next lower dose.
12 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) of Selinexor
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Time of Maximum Observed Concentration in Plasma (Tmax) of Selinexor
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Area Under the Concentration Time Curve From the Time of Dosing to Time in Plasma (AUC0-t) of Selinexor
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Area Under the Concentration Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Selinexor
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Elimination Half-Life (t1/2) of Selinexor
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Apparent Total Body Clearance (CL/F) of Selinexor
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Apparent Volume of Distribution of Selinexor (Vd/F)
Time frame: Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes
Number of Participants With Best Overall Response (BOR)
Time frame: Up to maximum duration of 45 months
Percentage of Participants With Objective Response
Time frame: Up to maximum duration of 45 months
Duration of Stable Disease (SD)
Time frame: From first dose of study drug administration to first documented evidence of disease recurrence or progression (maximum duration of 45 months)
Progression-free Survival (PFS)
Time frame: From start of study drug administration until PD or discontinuation from the study or death (maximum duration of 45 months)
Overall Survival (OS)
Time frame: From first dose of study drug administration to date of death (maximum duration of 45 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28630120Machlus KR, Wu SK, Vijey P, Soussou TS, Liu ZJ, Shacham E, Unger TJ, Kashyap T, Klebanov B, Sola-Visner M, Crochiere M, Italiano JE Jr, Landesman Y. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood. 2017 Aug 31;130(9):1132-1143. doi: 10.1182/blood-2016-11-752840. Epub 2017 Jun 19.
- Individual participant dataSharing planned: Yes
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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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selinexor and Acetaminophen in people with Solid Tumor, run by Karyopharm Therapeutics Inc at 6 sites in 3 countries.
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 13 inclusion and 2 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: finished, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Canada, Denmark. 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?
Yes. Results are posted in the registry (first posted 30 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) (time frame: From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)). The study lists 5 primary outcomes in all. 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 NCT01607905, which also lists 1 linked publication.
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 26 Jan 2023.