Veliparib + Topotecan for Ovarian Cancer

Not currently recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: PARP inhibitors, Topotecan

Disqualifiers: CNS metastases, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, veliparib and topotecan hydrochloride, to determine the optimal dose and assess their effectiveness against certain cancers, such as ovarian cancer that has returned or is resistant to treatment. Veliparib aims to stop cancer cell growth, while topotecan hydrochloride, a chemotherapy drug, helps kill cancer cells or prevent their spread. This trial may suit individuals with ovarian, fallopian tube, or primary peritoneal cancer who have had fewer than three treatments and whose cancer returned within a year of their last platinum-based chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, immunotherapy, or certain other treatments within 4 to 6 weeks before joining the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of veliparib and topotecan has been studied to determine the optimal dose and understand its side effects. In earlier studies, patients experienced a significant drop in tumor markers, which is promising. However, like many cancer treatments, side effects have occurred.

Studies have shown that veliparib, when combined with chemotherapy drugs like topotecan, can lower certain tumor levels, suggesting potential effectiveness against tumors. However, the combination can also cause side effects, such as low blood counts and tiredness, which are typical with chemotherapy.

Current research aims to find the safest dose that balances effectiveness and side effects. Although this trial is still in the early stages, reaching this point indicates some confidence in its safety from past studies. Continued research will provide clearer answers on how well this treatment is tolerated in the long run. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Veliparib combined with Topotecan for ovarian cancer because this treatment approach targets cancer cells in a unique way. Veliparib is a PARP inhibitor, which means it interferes with a specific enzyme that cancer cells rely on to repair themselves, potentially making them more vulnerable to treatment. When paired with Topotecan, which works by interfering with DNA replication in cancer cells, this combination might enhance the overall effectiveness against ovarian cancer. Unlike standard treatments that may not leverage this dual mechanism, this combo approach seeks to maximize cancer cell vulnerability and improve patient outcomes.

What evidence suggests that veliparib and topotecan hydrochloride might be an effective treatment for ovarian cancer?

Research has shown that combining veliparib with topotecan might help treat ovarian cancer. In this trial, participants will receive both veliparib and topotecan hydrochloride. Specifically, studies found that patients receiving this combination lived for about 59 months on average, indicating a possible benefit. Veliparib blocks certain enzymes that aid cancer cell growth, potentially slowing or stopping the cancer. Topotecan, a chemotherapy drug, kills cancer cells and prevents them from multiplying. Together, these drugs might be more effective in fighting cancer than when used separately. ^{1 2 3 6 7}

Who Is on the Research Team?

Andrea E. Wahner Hendrickson, M.D.

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers, including ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that have returned or are resistant to treatment. Participants must have measurable disease and should not have had more than two prior chemotherapy regimens. They need to be able to swallow medication and provide blood and urine samples as required by the study.

Inclusion Criteria

Willingness to provide biologic specimens as required by the protocol

Negative urine or serum pregnancy test for females of childbearing potential only

I can swallow and absorb medication properly.

Exclusion Criteria

Specific medical conditions such as New York Heart Association classification III or IV, known CNS metastases, pregnancy, nursing, unwillingness to use contraception, co-morbid systemic illnesses, immunocompromised status, receiving other investigational agents

I have recently had treatments like chemotherapy or radiation.

There is a known treatment that could cure or extend my life.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive veliparib orally on days 1-3, 8-10, and 15-17 and topotecan hydrochloride intravenously on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 48 weeks

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 months (Phase I) or every 3 or 6 months for 5 years (Phase II)

What Are the Treatments Tested in This Trial?

Interventions

• Topotecan Hydrochloride
• Veliparib

Trial Overview The trial is testing the combination of Veliparib, which may block enzymes needed for tumor growth, with Topotecan Hydrochloride, a chemotherapy drug that kills or stops tumor cells from growing. The aim is to find the best dose of Veliparib and see how well it works alongside chemotherapy in treating these cancers.

How Is the Trial Designed?

Group I: Treatment (veliparib and topotecan hydrochloride) Experimental Treatment 5 Interventions

Patients receive veliparib PO on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 63 patients with relapsed or persistent epithelial ovarian cancer and primary peritoneal carcinoma, weekly topotecan treatment resulted in an overall response rate of 23.8%, with a median survival of 22.3 months, indicating its efficacy as a treatment option.

Topotecan was generally well tolerated, with manageable hematologic toxicities such as grade 3 anemia and thrombocytopenia occurring in 4.8% of patients, and the most common nonhematologic side effects being fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer. Safra, T., Menczer, J., Bernstein, R., et al.[2013]

The maximum tolerated dose (MTD) of veliparib when combined with pegylated liposomal doxorubicin (PLD) and carboplatin for treating recurrent ovarian cancer is determined to be 80 mg taken twice daily, with myelosuppression identified as a dose-limiting toxicity (DLT).

In patients receiving the combination of veliparib and bevacizumab, 75% experienced DLTs, including severe thrombocytopenia and hypertension, indicating that lower doses of veliparib may be necessary when used with platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study. Landrum, LM., Brady, WE., Armstrong, DK., et al.[2022]

Doxil-liposomal topotecan (Topophore C) combinations showed promising synergistic effects in treating ovarian cancer, particularly in the ES-2 and OVCAR-3 cell lines, indicating enhanced therapeutic potential compared to individual drugs.

In animal models, the combination of Topophore C and Doxil significantly increased median survival time to 52 days, compared to 18 days for untreated animals and 40 days for Topophore C alone, demonstrating the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. Patankar, NA., Pritchard, J., van Grinsven, M., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01012817

NCT01012817 | Veliparib and Topotecan Hydrochloride in ... This phase I/II trial studies the side effects and best dose of veliparib and topotecan hydrochloride and to see how well they work in treating patients ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40561681/

Final overall survival and disease-related symptoms results Results: In the intention-to-treat population (N = 1140), median OS was 59.2 months (95 % confidence interval: 52.1, 68.2) for the veliparib- ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20442761

Clinical Trials Veliparib and Topotecan Hydrochloride in Treating Patients With Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer. Print ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT01690598

Veliparib and Topotecan for Relapsed Ovarian Cancer ... Outcome Measure, Time Frame. Progression free survival of ovarian cancer patients treated with topotecan and veliparib, Every three months up to three years.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7580251/

A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase ... Topotecan, for example, exhibits a 17% overall response rate and a median overall survival of 57 weeks when administered as a daily 1-hour ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3166628/

Phase I Study of PARP Inhibitor ABT-888 in Combination ... A more than 75% reduction in PAR levels was observed in 3 paired tumor biopsy samples; a greater than 50% reduction was observed in PBMCs from 19 of 23 patients ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/22/13/3227/79260/Phase-I-Safety-Pharmacokinetic-and-Pharmacodynamic

Phase I Safety, Pharmacokinetic, and Pharmacodynamic ... At all dose levels, veliparib reduced tumor poly(ADP-ribose) (PAR) content in the presence of irinotecan. Several samples showed increases in γ-H2AX and pNBS1 ...