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

NCT ID: NCT05983276

Last Updated: 2024-02-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-16
• Study Completion Date: 2031-08-28

Brief Summary

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.

Detailed Description

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Decitabine / Selinexor/ Carboplatin / Paclitaxel

C1:

Days 1-5: Decitabine 10 mg/m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2 Days 13, 20, and 27: paclitaxel 80 mg/m2 For a single 28 day cycle

Assess Response toxicities and immune effector cell changes

C2-C6:

Days 1-5: Decitabine 10 mg/m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2 Day 7 and weekly thereafter (day 14, 21, 28, 35…) Selinexor 60 mg PO Days 13, 20, and 27: paclitaxel 80 mg/m2 each given x five 28 day cycles

Assess responses by exam, CT scan and blood tests, assess toxicities, and immune effector cell changes as well as progression and overall survival

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.

Paclitaxel

Intervention Type: DRUG

Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."

Selinexor

Intervention Type: DRUG

Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.

Interventions

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.

Intervention Type: DRUG

Carboplatin

Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.

Intervention Type: DRUG

Paclitaxel

Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."

Intervention Type: DRUG

Selinexor

Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.

Intervention Type: DRUG

Other Intervention Names

Dacogen; Paraplatin; Abraxane; Xpovio, Nexpovio

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Patrick Stiff

Senior Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick L Stiff, MD

Role: PRINCIPAL_INVESTIGATOR

Loyola University

Locations

Loyola University Medical Center

Maywood, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Patrick Stiff, MD

Role: CONTACT

pstiff@lumc.edu

708-327-3148

Agnes Natonton, RN

Role: CONTACT

anatont@luc.edu

708-327-3383

Facility Contacts

Patrick Stiff, MD

Role: primary

pstiff@lumc.edu

708-327-3148

Jennifer Guevara, RN

Role: backup

jguevara@luc.edu

708-327-3239

Other Identifiers

215615

Identifier Type: -

Identifier Source: org_study_id