Ovarian CancerPhase 1NCT02269293
Selective Inhibitor of Nuclear Export, Selinexor (KPT-330) in Combination With Paclitaxel and Carboplatin in Patients With Advanced Ovarian or Endometrial Cancers
A Phase 1 study testing Paclitaxel, Carboplatin and Selinexor in people with Ovarian Cancer and Endometrial Cancer, run by Memorial Sloan Kettering Cancer Center at 3 sites in United States.
Trial summary
The purpose of this study is to test the safety of the investigational drug, selinexor (KPT-330), in combination with carboplatin and paclitaxel chemotherapy, where paclitaxel will be given at two different dosing schedules and selinexor will be given at two different dosing schedules. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Endometrial Cancer
- What is being tested?
- Paclitaxel, Carboplatin and Selinexor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Oct 2014to 20 Apr 2021
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have MSKCC pathologically confirmed diagnosis of one of the following tumor types:
- Ovarian, fallopian tube or primary peritoneal cancer, Ovarian carcinosarcoma, Endometrial cancer, Endometrial carcinosarcoma
- All patients with ovarian, fallopian tube or primary peritoneal cancer and ovarian carcinosarcoma must have recurrent disease, and only one prior line of chemotherapy that must have been platinum-based chemotherapy for the management of primary disease. This initial platinum-based treatment may have included intraperitoneal therapy, consolidation/maintenance and/or biologic/targeted agents (e.g., bevacizumab, PARP inhibitor) as part of first-line treatment.
- Patients with endometrial cancer or endometrial carcinosarcoma may either be chemotherapy naive OR have had one prior line of chemotherapy that must have been a platinum-based chemotherapy regimen in the adjuvant or advanced/recurrent setting. The initial platinum-based treatment may have included consolidation/maintenance and/or biologic/targeted agents as part of first-line treatment. Patients entering the trial chemotherapy naive MUST have Stage IVB or recurrent disease AND have disease that is not amenable to curative intent.
- Patients must have measurable disease (RECIST 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI.
- Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
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- Be at least 18 years of age.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Have adequate bone marrow, renal, hepatic and neurologic functions as defined by the following:
- Bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL
- Renal function:
- Creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 30 mL/min (Cockcroft-Gault calculation)
- Hepatic function:
- Bilirubin ≤ 1.5 x ULN
- AST and ALT ≤ 3 x ULN (less than or equal to 5 x upper limit of normal for patients with liver involvement of their cancer) (ULN = institutional/laboratory upper limit of normal; LLN = institutional/laboratory lower limit of normal)
- Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1.
- Patients must have recovered from effects of recent surgery, radiotherapy, chemotherapy or biologic/targeted therapy to baseline or CTCAE less than or equal to Grade 1 (excluding alopecia or other non-clinically significant AE's).
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study treatment initiation.
- Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted therapy and immunologic therapy, must be discontinued at least 3 weeks prior to study treatment initiation.
- Any investigation agents must be discontinued at least 30 days prior to study treatment initiation.
- Any prior radiation therapy must be discontinued at least 4 weeks prior to study treatment initiation.
- At least 4 weeks must have lapsed since major surgery (e.g., laparotomy, laparoscopy, thoracotomy, video assisted thoracoscopy) prior to study treatment initiation.
- Patients must be willing and able to swallow oral tablets.
- Patients must have signed an approved informed consent and authorization permitting the release of personal health information.
- Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. Sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug. Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects.
Who cannot join
- Patients who are pregnant or nursing.
- Patient who have had previous treatment with selinexor.
- Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures which are not controlled, any brain metastases and/or epidural disease, or history of cerebrovascular accident (CVA, stroke) within six months prior to the first date of study treatment.
- Patients requiring drainage gastrostomy (e.g., drainage PEG tube) and/or parenteral hydration and/or nutrition.
- Patients with clinically significant cardiovascular disease. This includes:
- Uncontrolled hypertension, defined as systolic greater than or equal to 160 mm Hg or diastolic greater than or equal to 100mm Hg despite antihypertensive medications.
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- Myocardial infarction or unstable angina within 6 months prior to the first date of study treatment.
- New York Heart Association (NYHA) Class II or greater congestive heart failure.
- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms. Note: if initial QTcF is found to be >500 ms, two additional ECG's separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is less than or equal to 500 ms, the subject meets eligibility in this regard.
- Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at undue risk
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first date of study treatment.
- Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memoral Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase 1 Open-label Study of the Selective Inhibitor of Nuclear Export, Selinexor (KPT-330) in Combination With Paclitaxel and Carboplatin in Patients With Advanced Ovarian or Endometrial Cancers
The purpose of this study is to test the safety of the investigational drug, selinexor (KPT-330), in combination with carboplatin and paclitaxel chemotherapy, where paclitaxel will be given at two different dosing schedules and selinexor will be given at two different dosing schedules. Carboplatin and paclitaxel chemotherapy is a commonly used therapy for the treatment of advanced or recurrent ovarian, fallopian tube, primary peritoneal, or endometrial cancer. The investigators want to find out what effects, good and/or bad, selinexor has on the patient and the cancer.
- Conditions
- Ovarian Cancer, Endometrial Cancer
- Being tested
- Paclitaxel, Carboplatin, Selinexor
- Keywords
- Selinexor (KPT-330), Paclitaxel, Carboplatin, 14-110
- Medical subject headings
- Ovarian Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
CarboplatinDrug
SelinexorDrug
Also called (KPT-330)
| Study group | Role | What they receive |
|---|---|---|
| Regimen 1 | Experimental | Paclitaxel 175 mg/m^2 IV, Day 1 (administered over approximately 3 hours) Carboplatin AUC 5 IV, Day 1 (administered over approximately 30 minutes) Selinexor (to be taken orally once daily on days 1, 4, 8, 11, 15, and 18 of each chemotherapy cycle) The selinexor tablet should not be crushed and/or chewed. Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Selinexor |
| Regimen 2 | Experimental | Paclitaxel 80 mg/m^2 IV, Days 1, 8, 15 (administered over approximately 1 hour) Carboplatin AUC 5 IV, Day 1 (administered over approximately 30 minutes) Selinexor orally (to be taken orally once daily on days 1, 4, 8, 11, 15, and 18 of each chemotherapy cycle) The selinexor tablet should not be crushed and/or chewed. Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Selinexor |
| Regimen 3 | Experimental | Paclitaxel 80 mg/m^2 IV, Days 1, 8, 15 (administered over approximately 1 hour) Carboplatin AUC 5 IV, Day 1 (administered over approximately 30 minutes) Selinexor orally (to be taken orally once weekly on days 1, 8, and 15 of each chemotherapy cycle) The selinexor tablet should not be crushed and/or chewed. Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Selinexor |
| Regimen 4 | Experimental | Paclitaxel and carboplatin will be delivered intravenously (IV) on day 1 of each cycle. Selinexor will be taken orally once a week on days 1, 8 and 15 of each chemotherapy cycle. Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum tolerated dose
The dose escalation phase will follow 3+3 scheme. The dose-limiting toxicities are based on the first cycle (21 days). All patients within a dose level will be observed for toxicity for one cycle prior entering new patients at the next dose level.
Measured: 1 year
Secondary outcomes (1)
response
as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1),
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2014 (estimated)
- Study start13 Oct 2014
- Primary completion20 Apr 2021
- Study completion20 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vicky Makker, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02269293
- Sponsor's protocol ID
- 14-110
- Status last verified
- Apr 2021
- First submitted
- 14 Oct 2014
- Last updated
- 23 Apr 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-label Study of the Selective Inhibitor of Nuclear Export, Selinexor (KPT-330) in Combination With Paclitaxel and Carboplatin in Patients With Advanced Ovarian or Endometrial Cancers
- ClinicalTrials.gov ID
- NCT02269293
- Acronym / sponsor ID
- 14-110
- Conditions
- Ovarian Cancer, Endometrial Cancer
- Keywords
- Selinexor (KPT-330), Paclitaxel, Carboplatin, 14-110
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 13 Oct 2014 (actual)
- Primary completion
- 20 Apr 2021 (actual)
- Study completion
- 20 Apr 2021 (actual)
- First posted
- 21 Oct 2014 (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.
The purpose of this study is to test the safety of the investigational drug, selinexor (KPT-330), in combination with carboplatin and paclitaxel chemotherapy, where paclitaxel will be given at two different dosing schedules and selinexor will be given at two different dosing schedules. Carboplatin and paclitaxel chemotherapy is a commonly used therapy for the treatment of advanced or recurrent ovarian, fallopian tube, primary peritoneal, or endometrial cancer. The investigators want to find out what effects, good and/or bad, selinexor has on the patient and the cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Regimen 1 | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: SelinexorPaclitaxel 175 mg/m^2 IV, Day 1 (administered over approximately 3 hours) Carboplatin AUC 5 IV, Day 1 (administered over approximately 30 minutes) Selinexor (to be taken orally once daily on days 1, 4, 8, 11, 15, and 18 of each chemotherapy cycle) The selinexor tablet should not be crushed and/or chewed. |
| Regimen 2 | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: SelinexorPaclitaxel 80 mg/m^2 IV, Days 1, 8, 15 (administered over approximately 1 hour) Carboplatin AUC 5 IV, Day 1 (administered over approximately 30 minutes) Selinexor orally (to be taken orally once daily on days 1, 4, 8, 11, 15, and 18 of each chemotherapy cycle) The selinexor tablet should not be crushed and/or chewed. |
| Regimen 3 | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: SelinexorPaclitaxel 80 mg/m^2 IV, Days 1, 8, 15 (administered over approximately 1 hour) Carboplatin AUC 5 IV, Day 1 (administered over approximately 30 minutes) Selinexor orally (to be taken orally once weekly on days 1, 8, and 15 of each chemotherapy cycle) The selinexor tablet should not be crushed and/or chewed. |
| Regimen 4 | Experimental | Drug: Paclitaxel, Drug: Carboplatin, Drug: SelinexorPaclitaxel and carboplatin will be delivered intravenously (IV) on day 1 of each cycle. Selinexor will be taken orally once a week on days 1, 8 and 15 of each chemotherapy cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients must have MSKCC pathologically confirmed diagnosis of one of the following tumor types:
- Ovarian, fallopian tube or primary peritoneal cancer, Ovarian carcinosarcoma, Endometrial cancer, Endometrial carcinosarcoma
- All patients with ovarian, fallopian tube or primary peritoneal cancer and ovarian carcinosarcoma must have recurrent disease, and only one prior line of chemotherapy that must have been platinum-based chemotherapy for the management of primary disease. This initial platinum-based treatment may have included intraperitoneal therapy, consolidation/maintenance and/or biologic/targeted agents (e.g., bevacizumab, PARP inhibitor) as part of first-line treatment.
- Patients with endometrial cancer or endometrial carcinosarcoma may either be chemotherapy naive OR have had one prior line of chemotherapy that must have been a platinum-based chemotherapy regimen in the adjuvant or advanced/recurrent setting. The initial platinum-based treatment may have included consolidation/maintenance and/or biologic/targeted agents as part of first-line treatment. Patients entering the trial chemotherapy naive MUST have Stage IVB or recurrent disease AND have disease that is not amenable to curative intent.
- Patients must have measurable disease (RECIST 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI.
Key exclusion criteria (13 listed)
- Patients who are pregnant or nursing.
- Patient who have had previous treatment with selinexor.
- Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures which are not controlled, any brain metastases and/or epidural disease, or history of cerebrovascular accident (CVA, stroke) within six months prior to the first date of study treatment.
- Patients requiring drainage gastrostomy (e.g., drainage PEG tube) and/or parenteral hydration and/or nutrition.
- Patients with clinically significant cardiovascular disease. This includes:
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 |
|---|---|---|
| Paclitaxel | Drug | Regimen 1, Regimen 2, Regimen 3, Regimen 4 |
| Carboplatin | Drug | Regimen 1, Regimen 2, Regimen 3, Regimen 4 |
| SelinexorAlso: (KPT-330) | Drug | Regimen 1, Regimen 2, Regimen 3, Regimen 4 |
Primary outcome
maximum tolerated dose
Time frame: 1 year
The dose escalation phase will follow 3+3 scheme. The dose-limiting toxicities are based on the first cycle (21 days). All patients within a dose level will be observed for toxicity for one cycle prior entering new patients at the next dose level.
1 secondary outcome
response
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2021.
- Memorial Sloan Kettering 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.
Vicky Makker, MD principal investigator
Memorial Sloan Kettering Cancer Center
3 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 Paclitaxel, Carboplatin and Selinexor in people with Ovarian Cancer and Endometrial Cancer, run by Memorial Sloan Kettering Cancer Center at 3 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 28 inclusion and 13 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 23 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
maximum tolerated dose (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2021.