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

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Primary Purpose

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Decitabine

Carboplatin

Paclitaxel

Selinexor

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian Cancer, Platinum Resistance, Relapsed/Refractory Epithelial, Fallopian Tube, Primary Peritoneal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Loyola University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Decitabine / Selinexor/ Carboplatin / Paclitaxel

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

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

Full Information

NCT ID

NCT05983276

First Posted

July 12, 2023

Last Updated

August 1, 2023

Sponsor

Loyola University

Collaborators

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT05983276

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

August 28, 2023 (Anticipated)

Primary Completion Date

August 28, 2030 (Anticipated)

Study Completion Date

August 28, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Loyola University

Collaborators

Karyopharm Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Decitabine / Selinexor/ Carboplatin / Paclitaxel

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Decitabine

Other Intervention Name(s)

Dacogen

Intervention Description

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

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Abraxane

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Selinexor

Other Intervention Name(s)

Xpovio, Nexpovio

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

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])

Description

To determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant disease as measured by response rates

Time Frame

6 months

Title

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

Description

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.

Time Frame

6 months

Title

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

Description

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

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Patrick Stiff, MD

Phone

708-327-3148

Email

pstiff@lumc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Agnes Natonton, RN

Phone

708-327-3383

Email

anatont@luc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patrick L Stiff, MD

Organizational Affiliation

Loyola University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Loyola University Medical Center

City

Maywood

State/Province

Illinois

ZIP/Postal Code

60153

Country

United States

Ovarian Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial