Decitabine and Selinexor in Combination to Reverse Drug Resistance With Standard Chemotherapy in Ovarian Cancer

Официальное название

Combination of the Hypomethylating Agent Decitabine and the Nuclear Export Receptor XPO-1 Inhibitor Selinexor to Reverse Platinum Resistance in Relapsed/Refractory Epithelial Ovarian Cancer

Обзор

The goal of this clinical trial is to learn about the side effects and effectiveness of this novel four-drug combination of chemotherapy (decitabine, selinexor, carboplatin and paclitaxel) on patients with relapsed ovarian, fallopian or primary peritoneal carcinoma. Recently the investigators have found that the combination of decitabine and selinexor, two Food and Drug Administration (FDA) approved chemotherapy agents, may prevent or reverse the development of drug resistance and further the remissions and duration of remissions with standard ovarian cancer chemotherapy with carboplatin and paclitaxel. As decitabine and selinexor are not FDA approved for the participant's cancer, these agents are investigational.

Подробное описание

Participants enrolled in this study protocol will receive therapy with decitabine followed by usual doses of carboplatin and paclitaxel for one cycle. If the participant tolerates this well, the selinexor will be added to the second and subsequent cycles of therapy given at 4-week intervals, in the out-patient setting. The participant will be asked to complete 9 study visits during their active therapy during each cycle: Days 1-5 of each cycle the participant will receive decitabine treatments over 1 hour, with carboplatin and paclitaxel given on day 6. Paclitaxel alone will continue weekly for 3 weeks on days 13, 20 and 27 of the 28-day cycle. The 5 days of daily decitabine therapy lasts about 1 hour and the carboplatin and paclitaxel treatment last 4 hours, with single agent paclitaxel being only 1 hour.

Selinexor is not added until cycle 2 and is given orally weekly on days 7, 14, 21, and 28 of the 28-day cycle. Weekly clinic visits are required for the first two cycles at the time paclitaxel is administered.

The participant's progress will be assessed and if a remission is achieved the participant would continue the therapy for up to 6 cycles.

Вмешательства

• Препарат Decitabine
  Decitabine is classified as hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow.
• Препарат Carboplatin
  Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.
• Препарат Paclitaxel
  Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."
• Препарат Selinexor
  Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.

Первичные конечные точки

• 40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3. [Срок оценки: 6 months]

Вторичные конечные точки (3)

• 40 participants evaluated to determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant recurrent disease as measured by response rates. Response rates (partial response [PR] and complete response [CR]) [Срок оценки: 6 months]
• 40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy. [Срок оценки: 6 months]
• 40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3. [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Participants must be greater than or equal to 18 years of age
• Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status PS less than or equal to 2.
• Participants must have histological or cytological proven epithelial ovarian cancer, fallopian tube or primary peritoneal carcinoma with relapse or disease progression after prior treatment by exam, computed tomography (CT), PET/CT, or magnetic resonance imaging (MRI) may be enrolled. All cell types including clear cell carcinoma are eligible.
• Participants must have failed or relapsed after a platinum and taxane containing combination
• Participants must have adequate hepatic function
• Participants must have adequate renal function
• Participants must be able to swallow and retain oral medications
• Participants must have measurable disease according to Gynecologic Cancer Intergroup CA125 criteria
• Participants with stable (for 2 months or longer), treated (by radiotherapy) CNS metastases are eligible
• Participants with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for greater than 8 weeks.

Критерии исключения

• Participants must not have received Selinexor or another XPO1 inhibitor previously.
• Participants must not have had any concurrent medical condition or disease (eg, uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.)
• Participants must not have uncontrolled active infection. Participants on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
• Participants must not have known intolerance, hypersensitivity, or contraindication to platinum or taxane therapy
• Participants must not have active, unstable cardiovascular function
• Participants must not have myocardial infarction within 3 months prior to starting
• Participants with untreated central nervous system (CNS) metastases are ineligible.
• Participants must not have had prior chemotherapy or radiation therapy
• Participants must not have DVT related to metastatic disease requiring ongoing anticoagulation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Loyola University Medical Center — Maywood

Идентификаторы

NCT: NCT05983276 · 215615

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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