Veliparib + Topotecan for Ovarian Cancer

Recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

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

88 Participants Needed

Trial Summary

What is the purpose of this trial?

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 with solid tumors, ovarian cancer that has come back or does not respond to treatment, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib with chemotherapy may kill more tumor cells.

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.

What data supports the effectiveness of the drug Veliparib + Topotecan for treating ovarian cancer?

Research shows that veliparib, when added to other chemotherapy drugs, improved the time patients lived without their cancer getting worse. Additionally, topotecan has been effective in treating ovarian cancer, even in patients who have undergone multiple treatments. ^{1 2 3 4 5}

Is the combination of Veliparib and Topotecan safe for humans?

In a Phase I trial, the combination of Veliparib and Topotecan was found to have a manageable safety profile in patients with solid tumors. The main side effect was severe neutropenia (a drop in white blood cells) lasting more than 5 days, but overall, the treatment was considered safe enough to warrant further study. ^{1 2 6 7 8}

What makes the drug Veliparib + Topotecan unique for ovarian cancer treatment?

The combination of Veliparib and Topotecan is unique because it combines a PARP inhibitor (Veliparib) with a topoisomerase I inhibitor (Topotecan), offering a novel mechanism of action compared to standard treatments like platinum-based therapies and taxanes. This combination may provide a new option for patients, especially those who have not responded to traditional therapies. ^{5 9 10 11 12}

Research Team

Andrea E. Wahner Hendrickson, M.D.

Principal Investigator

Mayo Clinic Cancer Center LAO

Eligibility Criteria

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

I can swallow and absorb medication properly.

Willingness to provide biologic specimens as required by the protocol

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Topotecan plus carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a meta-analysis of randomized controlled trials. [2015]

4. United States 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. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Salvage therapy with topotecan in heavily pretreated ovarian cancer patients. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies. [2022]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Emerging role of topotecan in front-line treatment of carcinoma of the ovary. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Topotecan: An Oncologist's View. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

A phase II study of two topotecan regimens evaluated in recurrent platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer: a Gynecologic Oncology Group Study (GOG 146Q). [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer. [2013]