What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, particularly PARP inhibitors like Talazoparib, often result in side effects such as anemia, nausea, fatigue, and thrombocytopenia. These side effects are generally manageable with dose modifications and supportive care. Investigational treatments like BET inhibitors (e.g., ZEN003694) are still being studied, but they may share similar side effects with other targeted therapies, including gastrointestinal disturbances and hematologic toxicities. Overall, the side effects of these treatments can vary in severity but are typically manageable with appropriate medical intervention.

What prior FDA approvals exist?

The FDA has approved several PARP inhibitors for the treatment of ovarian cancer, including Olaparib, Niraparib, and Rucaparib. These drugs are primarily used as maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer, particularly those with BRCA mutations. Olaparib was one of the first PARP inhibitors approved and has shown significant improvement in progression-free survival. Niraparib and Rucaparib have also demonstrated efficacy in similar settings. These approvals highlight the importance of PARP inhibitors in the management of ovarian cancer, especially for patients with specific genetic mutations.

What other types of research exist?

Promising alternatives for ovarian cancer treatment in 2024 include: 1) Olaparib, another PARP inhibitor, which has shown efficacy in BRCA-mutated ovarian cancer. 2) Niraparib, a PARP inhibitor effective in both BRCA-mutated and non-mutated cases. 3) Pembrolizumab, an immunotherapy for patients with high microsatellite instability or mismatch repair deficiency. 4) Combination therapies such as Olaparib with Bevacizumab, which have shown improved progression-free survival in clinical trials.

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PARP Inhibitor

ZEN003694 + Talazoparib for Ovarian Cancer

Phase 2

Recruiting

Led By Haider Mahdi, MD

Research Sponsored by Haider Mahdi

Eligibility Criteria Checklist

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

Must have

Known BRCA1/2 status

Prior therapy with PARPi either as maintenance or therapeutic settings

Must not have

Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug

Radiation to >25% of the bone marrow

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two oral drugs, ZEN003694 and talazoparib, in patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. ZEN003694 helps stop cancer cells from growing, while talazoparib blocks an enzyme that cancer cells need to repair themselves. The goal is to see how well these drugs work together in this specific group of patients.

Who is the study for?

This trial is for women over 18 with recurrent ovarian, fallopian tube, or primary peritoneal carcinoma. Participants must have had prior therapy with PARPi, any number of previous cancer treatments, measurable disease, known BRCA1/2 status and meet specific health criteria including adequate blood counts and organ function. They cannot be pregnant or breastfeeding and must use effective contraception if of childbearing potential.

What is being tested?

The study tests the combination of two oral drugs: ZEN003694 and Talazoparib given daily in cycles lasting 28 days to treat recurrent ovarian cancer. It's an open-label Phase 2 trial which means everyone gets the treatment and knows what they are receiving.

What are the potential side effects?

While not explicitly listed in your information provided, common side effects for similar cancer therapies may include nausea, fatigue, low blood cell counts leading to increased infection risk or bleeding problems, liver function changes, digestive issues and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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I know my BRCA1/2 gene status.

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I have been treated with PARP inhibitors before.

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I am a woman aged 18 or older.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My ovarian cancer has come back, regardless of its response to platinum-based chemotherapy.

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I have been diagnosed with cancer in my ovary, fallopian tube, or the lining of my abdomen.

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I am not breastfeeding and will not breastfeed during the study or for 7 months after.

Exclusion Criteria

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

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I have not had a heart attack or unstable chest pain in the last 6 months.

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More than a quarter of my bone marrow has been exposed to radiation.

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I have not had major surgery, except for diagnosis, dental work, or stenting, in the last 4 weeks.

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I am taking blood thinners, but not oral Factor Xa or IIa inhibitors.

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I do not have any major health issues that could affect my safety or participation in the study.

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I do not have serious heart problems like uncontrolled arrhythmia or severe heart failure.

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I have been treated with an experimental BET inhibitor before.

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I do not have any non-healing wounds, ulcers, or bone fractures.

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I have been diagnosed with myelodysplastic syndrome.

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I have been diagnosed with ovarian carcinosarcoma.

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I am not currently using, nor plan to use, strong medication that affects enzyme CYP3A4 or CYP1A2.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response

Secondary study objectives

Adverse events at least possibly related to treatment

Duration of Response

Overall survival (OS)

+1 more

Side effects data

From 2019 Phase 1 & 2 trial • 75 Patients • NCT02711956

58%

Visual impairment

52%

Nausea

42%

Fatigue

32%

Decreased appetite

32%

Dysgeusia

19%

Thrombocytopenia

16%

Diarrhea

10%

Taste disorder

10%

Weight decreased

10%

Photosensitivity reaction

10%

Constipation

10%

Photopsia

10%

Vomiting

10%

Dizziness

10%

Blood creatinine increased

Intervertebral discitis

Acute kidney injury

Musculoskeletal pain

Myocardial ischaemia

Spinal cord compression

Rash maculopapular

100%

80%

60%

40%

20%

Study treatment Arm

DE/DC A+B 96 mg ZEN003694 + Enzalutamide

DE A+B 36 mg ZEN003694 + Enzalutamide

DE/DC A+B 48 mg ZEN003694 + Enzalutamide

DE A+B 60 mg ZEN003694 + Enzalutamide

DE A+B 72 mg ZEN003694 + Enzalutamide

DE A+B 120 mg ZEN003694 + Enzalutamide

DE A+B 144 mg ZEN003694 + Enzalutamide

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: ZEN003694 + TalazoparibExperimental Treatment2 Interventions

ZEN003694: 48.0 mg daily (oral) in 28-day cycles Talazoparib: 0.75 mg daily (oral) at the same time as ZEN003694

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ZEN003694

2016

Completed Phase 2

~120

Talazoparib

2021

Completed Phase 2

~2810

0 / 18Eligibility 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

PARP inhibitors like Talazoparib work by inhibiting the poly(ADP-ribose) polymerase enzyme, essential for repairing single-strand DNA breaks, leading to cancer cell death, particularly in cells with BRCA mutations. BET inhibitors like ZEN003694 target proteins that regulate gene expression, disrupting the survival and proliferation of cancer cells. These targeted therapies offer ovarian cancer patients more personalized and potentially more effective treatment options with fewer side effects compared to traditional chemotherapy.