Ovarian CancerPhase 2NCT05983276
Decitabine and Selinexor in Combination to Reverse Drug Resistance With Standard Chemotherapy in Ovarian Cancer
A Phase 2 study testing Decitabine, Carboplatin and Paclitaxel in people with Ovarian Cancer, run by Loyola University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Decitabine, Carboplatin and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2023to 28 Aug 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Patrick Stiff, MD, 708-327-3148, pstiff@lumc.edu
Jennifer Guevara, RN, 708-327-3239, jguevara@luc.edu
About this study
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
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.
Read the 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
- Being tested
- Decitabine, Carboplatin, Paclitaxel, Selinexor
- Keywords
- Ovarian Cancer, Platinum Resistance, Relapsed/Refractory Epithelial, Fallopian Tube, Primary Peritoneal Cancer
- Medical subject headings
- Ovarian Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
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.
CarboplatinDrug
Also called Paraplatin
Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.
PaclitaxelDrug
Also called Abraxane
Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."
SelinexorDrug
Also called Xpovio, Nexpovio
Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Decitabine; Drug: Carboplatin; Drug: Paclitaxel; Drug: Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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])
To determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant disease as measured by response rates
Measured: 6 months
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.
Measured: 6 months
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2023
- Study start16 Nov 2023
- Primary completion28 Aug 2030 (estimated)
- Study completion28 Aug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Responsible party
- Principal investigator, Patrick Stiff, Loyola University
- Investigators
- Patrick L Stiff, MD, Principal investigator, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05983276
- Sponsor's protocol ID
- 215615
- Status last verified
- Feb 2024
- First submitted
- 12 Jul 2023
- Last updated
- 8 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05983276
- Acronym / sponsor ID
- 215615
- Conditions
- Ovarian Cancer
- Keywords
- Ovarian Cancer, Platinum Resistance, Relapsed/Refractory Epithelial, Fallopian Tube, Primary Peritoneal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Study start
- 16 Nov 2023 (actual)
- Primary completion
- 28 Aug 2030 (estimated)
- Study completion
- 28 Aug 2031 (estimated)
- First posted
- 9 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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
| Arm | Type | Receives |
|---|---|---|
| Decitabine / Selinexor/ Carboplatin / Paclitaxel | Experimental | Drug: Decitabine, Drug: Carboplatin, Drug: Paclitaxel, Drug: SelinexorC1: 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: DacogenDecitabine 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. | Drug | Decitabine / Selinexor/ Carboplatin / Paclitaxel |
| CarboplatinAlso: ParaplatinCarboplatin is classified as an alkylating agent that is used to treat ovarian cancer. | Drug | Decitabine / Selinexor/ Carboplatin / Paclitaxel |
| PaclitaxelAlso: AbraxanePaclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent." | Drug | Decitabine / Selinexor/ Carboplatin / Paclitaxel |
| SelinexorAlso: Xpovio, NexpovioSelinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells. | Drug | Decitabine / Selinexor/ Carboplatin / Paclitaxel |
Primary outcome
40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3.
Time frame: 6 months
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
3 secondary outcomes
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])
Time frame: 6 months
40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy.
Time frame: 6 months
40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3.
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Patrick L Stiff, MD principal investigator
Loyola University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Decitabine, Carboplatin and Paclitaxel in people with Ovarian Cancer, run by Loyola University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Patrick Stiff, MD (708-327-3148, pstiff@lumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2024; AzTrials last refreshed its copy on 7 Nov 2026.