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

NCT05983276 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 215615
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Keywords

Ovarian Cancer; Platinum Resistance; Relapsed/Refractory Epithelial; Fallopian Tube; Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (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])

  6 months

• 40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy.

  6 months

• 40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3.

  6 months

Study Arms (1)

Decitabine / Selinexor/ Carboplatin / Paclitaxel

EXPERIMENTAL

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

Drug: Decitabine; Drug: Carboplatin; Drug: Paclitaxel; Drug: Selinexor

Interventions

Decitabine 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.

Also known as: Dacogen

Decitabine / Selinexor/ Carboplatin / Paclitaxel

Carboplatin DRUG

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

Also known as: Paraplatin

Decitabine / Selinexor/ Carboplatin / Paclitaxel

Paclitaxel DRUG

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

Also known as: Abraxane

Decitabine / Selinexor/ Carboplatin / Paclitaxel

Selinexor DRUG

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

Also known as: Xpovio, Nexpovio

Decitabine / Selinexor/ Carboplatin / Paclitaxel

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Loyola University: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Recurrence

Interventions

Decitabine; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Patrick L Stiff, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Stiff, MD

CONTACT

708-327-3148; pstiff@lumc.edu

Agnes Natonton, RN

CONTACT

708-327-3383; anatont@luc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Professor

Model Details: Once selected for therapy, the participant will receive the following treatment in the outpatient setting: 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. 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

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: August 9, 2023
• Study Start: November 16, 2023
• Primary Completion (Estimated): August 28, 2030
• Study Completion (Estimated): August 28, 2031
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

US (1)