What side effects are associated with this type of intervention?

The four-drug combination of Decitabine, Selinexor, Carboplatin, and Paclitaxel for ovarian cancer treatment is associated with several side effects. Decitabine and Selinexor can cause neutropenia and other hematologic toxicities. Carboplatin and Paclitaxel, standard chemotherapy agents, commonly lead to neutropenia, thrombocytopenia, sensory neuropathy, nausea, and vomiting. Combining these drugs may increase the risk and severity of these side effects, requiring careful monitoring and supportive care.

What prior FDA approvals exist?

Carboplatin and Paclitaxel are FDA-approved standard chemotherapeutic agents commonly used in the treatment of ovarian cancer, often in combination due to their synergistic effects. Decitabine and Selinexor, while FDA-approved for other indications, are being investigated for their potential to prevent or reverse drug resistance in ovarian cancer. This novel combination aims to enhance the efficacy of standard chemotherapy regimens by incorporating these agents to potentially improve outcomes in relapsed or refractory ovarian cancer cases.

What other types of research exist?

Promising novel alternatives for ovarian cancer treatment in 2024 include: <ol> <li>Bevacizumab combined with platinum-based chemotherapy (e.g., Carboplatin and Paclitaxel) followed by Bevacizumab maintenance therapy.</li> <li></li> </ol> PARP inhibitors (e.g., Olaparib, Niraparib, Rucaparib) for maintenance therapy, especially in patients with BRCA mutations or homologous recombination repair (HRR) deficiencies. 3. Combination of Azacitidine with Gilteritinib, although further data is awaited before widespread use outside clinical trials. 4. Low-dose Cytarabine (LoDAC) combined with Venetoclax or Glasdegib for patients not suitable for HMA-based treatments.

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Alkylating agents

Decitabine + Selinexor for Ovarian Cancer

Phase 2

Recruiting

Led By Patrick L Stiff, MD

Research Sponsored by Loyola University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must be greater than or equal to 18 years of age

Participants must be able to swallow and retain oral medications

Must not have

Participants must not have known intolerance, hypersensitivity, or contraindication to platinum or taxane therapy

Participants must not have received Selinexor or another XPO1 inhibitor previously

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of four drugs to treat patients whose ovarian, fallopian tube, or primary peritoneal cancer has returned. The treatment aims to kill cancer cells and prevent them from becoming resistant. The drugs are administered in a specific sequence to maximize effectiveness.

Who is the study for?

This trial is for adults with relapsed ovarian, fallopian tube, or primary peritoneal carcinoma who can take oral meds and have measurable disease. They must have had platinum and taxane treatments before but now show disease progression. Stable CNS metastases treated by radiotherapy are okay; active Hep B is allowed if on antivirals for 8+ weeks.

What is being tested?

The study tests a four-drug combo (decitabine, selinexor, carboplatin, paclitaxel) to see if it can prevent drug resistance in ovarian cancer chemotherapy. Decitabine and selinexor may help extend remission when combined with standard chemo drugs carboplatin and paclitaxel.

What are the potential side effects?

Possible side effects include reactions typical of chemotherapy such as nausea, fatigue, blood cell count changes leading to increased infection risk or bleeding problems, liver or kidney function issues, and potential allergic reactions to the medication components.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I can swallow and keep down pills.

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My kidneys are working well.

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I can take care of myself but might not be able to do heavy physical work.

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My cancer did not respond or came back after treatment with platinum and taxane.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not allergic or sensitive to platinum or taxane treatments.

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I have never taken Selinexor or similar medications.

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I do not need ongoing blood thinners for a clot related to my cancer.

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My heart condition is stable.

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I have not had chemotherapy or radiation therapy before.

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I do not have untreated brain metastases.

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I do not have any uncontrolled health conditions like high blood pressure or diabetes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

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

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

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])

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Decitabine / Selinexor/ Carboplatin / PaclitaxelExperimental Treatment4 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Selinexor

2020

Completed Phase 3

~1730

Paclitaxel

2011

Completed Phase 4

~5450

Decitabine

2004

Completed Phase 3

~1720

Carboplatin

2014

Completed Phase 3

~6120

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The four-drug combination chemotherapy for ovarian cancer includes Decitabine, Selinexor, Carboplatin, and Paclitaxel. Decitabine is a DNA methyltransferase inhibitor that reactivates silenced genes, potentially reversing drug resistance. Selinexor is a selective inhibitor of nuclear export, which traps tumor suppressor proteins in the nucleus, enhancing their anti-cancer activity. Carboplatin, a platinum-based drug, causes DNA crosslinking and damage, leading to cell death. Paclitaxel stabilizes microtubules, preventing cell division. This combination is significant for ovarian cancer patients as it targets multiple pathways, potentially overcoming resistance and improving treatment efficacy.

A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship.