Selective Inhibitor of Nuclear Export, Selinexor (KPT-330) in Combination With Paclitaxel and Carboplatin in Patients With Advanced Ovarian or Endometrial Cancers

NCT02269293 | Completed Phase 1

• 1 other identifier: 14-110
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief 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. 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

Keywords

Selinexor (KPT-330); Paclitaxel; Carboplatin; 14-110

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• response

  1 year

Study Arms (4)

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.

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.

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.

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.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Selinexor

Interventions

Paclitaxel DRUG

Regimen 1; Regimen 2; Regimen 3; Regimen 4

Carboplatin DRUG

Regimen 1; Regimen 2; Regimen 3; Regimen 4

Selinexor DRUG

Also known as: (KPT-330)

Regimen 1; Regimen 2; Regimen 3; Regimen 4

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (3)

Memoral Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms

Interventions

Paclitaxel; Carboplatin; selinexor

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Vicky Makker, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 21, 2014
• Study Start: October 13, 2014
• Primary Completion: April 20, 2021
• Study Completion: April 20, 2021
• Last Updated: April 23, 2021

Record last verified: 2021-04

Locations

US (3)