Trial Title:
Decitabine and Selinexor in Combination to Reverse Drug Resistance With Standard Chemotherapy in Ovarian Cancer
NCT ID:
NCT05983276
Condition:
Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Paclitaxel
Carboplatin
Decitabine
Conditions: Keywords:
Ovarian Cancer
Platinum Resistance
Relapsed/Refractory Epithelial
Fallopian Tube
Primary Peritoneal Cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention 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
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Decitabine
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.
Arm group label:
Decitabine / Selinexor/ Carboplatin / Paclitaxel
Other name:
Dacogen
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.
Arm group label:
Decitabine / Selinexor/ Carboplatin / Paclitaxel
Other name:
Paraplatin
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule
agent."
Arm group label:
Decitabine / Selinexor/ Carboplatin / Paclitaxel
Other name:
Abraxane
Intervention type:
Drug
Intervention name:
Selinexor
Description:
Selinexor is in a class of medications called selective inhibitors of nuclear export
(SINE). It works by killing cancer cells.
Arm group label:
Decitabine / Selinexor/ Carboplatin / Paclitaxel
Other name:
Xpovio, Nexpovio
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Loyola University Medical Center
Address:
City:
Maywood
Zip:
60153
Country:
United States
Status:
Recruiting
Contact:
Last name:
Patrick Stiff, MD
Phone:
708-327-3148
Email:
pstiff@lumc.edu
Contact backup:
Last name:
Jennifer Guevara, RN
Phone:
708-327-3239
Email:
jguevara@luc.edu
Investigator:
Last name:
Ronald Potkul, MD
Email:
Sub-Investigator
Investigator:
Last name:
Margaret Liotta, MD
Email:
Principal Investigator
Investigator:
Last name:
Abigal Winder, MD
Email:
Sub-Investigator
Start date:
November 16, 2023
Completion date:
August 28, 2031
Lead sponsor:
Agency:
Loyola University
Agency class:
Other
Collaborator:
Agency:
Karyopharm Therapeutics Inc
Agency class:
Industry
Source:
Loyola University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05983276
