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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05983276
• Other study ID #: 215615
• Status: Recruiting
• Phase: Phase 2
• Start date: November 16, 2023
• Est. completion date: August 28, 2031

Study information

• Verified date: February 2024
• Source: Loyola University
• Contact: Patrick Stiff, MD
• Phone: 708-327-3148
• Email: pstiff[@]lumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 28, 2031
• Est. primary completion date: August 28, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• 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.
• Carboplatin
Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.
• Paclitaxel
Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."
• Selinexor
Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Karyopharm Therapeutics Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3.	To determine the safety of two agents in combination to reverse platinum resistance in ovarian cancer: the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, selinexor, combined with carboplatin and paclitaxel in patients with relapsed/refractory epithelial ovarian carcinoma	6 months
Secondary	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])	To determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant disease as measured by response rates	6 months
Secondary	40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy.	This is an exploratory endpoint to determine if there is a potential immune enhancement of this combination on numbers of Immune T and B cells after therapy (15% or higher increase in cell numbers/mm3) when compared to pre-treatment values and whether this correlates to response rates.	6 months
Secondary	40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3.	To determine the tolerability of two agents that reverse platinum sensitivity in ovarian cancer, the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, Selinexor, combined with carboplatin and Taxol in patients with relapsed/refractory epithelial ovarian carcinoma	6 months