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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paclitaxel | Drug |
| ||
| Carboplatin |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| response | as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1), | 1 year |
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Inclusion Criteria:
Ovarian, fallopian tube or primary peritoneal cancer, Ovarian carcinosarcoma, Endometrial cancer, Endometrial carcinosarcoma
Bone marrow function:
Renal function:
Hepatic function:
Exclusion Criteria:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Vicky Makker, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memoral Sloan Kettering Monmouth | Middletown | New Jersey | 07748 | United States | ||
| Memorial Sloan Kettering Westchester |
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| Label | URL |
|---|---|
| Memorial Sloan Kettering Cancer Center | View source |
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|
| Drug |
|
| Selinexor | Drug |
|
|
| Harrison |
| New York |
| 10604 |
| United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D014594 | Uterine Neoplasms |
| D014591 | Uterine Diseases |
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| ID | Term |
|---|---|
| D017239 | Paclitaxel |
| D016190 | Carboplatin |
| C585161 | selinexor |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
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