Cisplatin + Veliparib for Breast Cancer

No longer recruiting at 948 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Cisplatin, PARP inhibitors

Disqualifiers: Hearing impairment, AML/MDS, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 48

Duration: Up to 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for certain types of breast cancer. Researchers aim to determine if adding veliparib, which prevents cancer cells from repairing themselves, enhances the effectiveness of the chemotherapy drug cisplatin (also known as Platinol). The trial focuses on patients with triple-negative breast cancer or a BRCA mutation, particularly if the cancer has recurred or spread to the brain. Individuals with these specific types of breast cancer are encouraged to consider participation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received chemotherapy within 14 days or any immunotherapy, biologic, or investigational drug within 28 days before joining the trial.

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

Research shows that using cisplatin with veliparib may help treat certain types of breast cancer. Veliparib is a drug that prevents cancer cells from repairing themselves. Studies have found that combining veliparib with cisplatin can effectively combat cancer.

Regarding safety, earlier studies have not identified a maximum safe dose of veliparib, suggesting it is generally well-tolerated. However, some patients experienced side effects such as low white blood cells (increasing infection risk), low red blood cells (anemia), and low platelets (important for clotting). These side effects were more severe for a smaller group of patients.

Overall, the combination is considered safe for most people, allowing them to handle the treatment without major issues. Prospective trial participants should consult a healthcare provider about possible side effects to understand what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of cisplatin and veliparib for breast cancer because it targets the cancer in a unique way. While standard treatments often focus on chemotherapy alone, this approach combines cisplatin, a powerful chemotherapy drug, with veliparib, a PARP inhibitor that helps prevent cancer cells from repairing their DNA. This combination aims to enhance the effectiveness of the treatment by making it harder for cancer cells to survive and multiply. Additionally, this method could potentially offer better outcomes for patients by exploiting vulnerabilities in the cancer's DNA repair mechanisms.

What evidence suggests that this trial's treatments could be effective for breast cancer?

In this trial, participants will receive either a combination of veliparib and cisplatin or cisplatin with a placebo. Research has shown that combining veliparib with cisplatin can lead to better outcomes for patients with BRCA-like metastatic triple-negative breast cancer. One study demonstrated that this combination allowed patients to live 5.9 months without cancer progression, compared to 4.2 months with cisplatin alone. Another study found that 35% of patients responded well to the treatment, with some experiencing complete or partial tumor shrinkage. Additionally, adding veliparib may extend survival for patients with advanced triple-negative breast cancer after starting treatment. These findings suggest that veliparib could enhance the effectiveness of cisplatin in certain breast cancer cases. ^{2 6 7 8 9}

Who Is on the Research Team?

Eve T Rodler

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or metastatic triple-negative breast cancer and/or BRCA mutation-associated breast cancer, which may include brain metastases. Participants must not be pregnant or nursing, agree to use contraception, have adequate organ function and no history of certain cancers or uncontrolled illnesses. Prior treatments must meet specific criteria.

Inclusion Criteria

Participants must have breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, or have a known harmful BRCA1 or BRCA2 gene mutation.

Patients of childbearing potential must not be pregnant (negative pregnancy test) or nursing due to the possibility of harm to a fetus or nursing infant from this treatment regimen; men and women of reproductive potential must have agreed to use an effective contraceptive method for 6 months after completion of study treatment

As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study had been entered in the system

Exclusion Criteria

I haven't had cisplatin or PARP inhibitors, but carboplatin over a year ago is okay.

I have not had chemotherapy in the last 14 days.

I do not have leukemia or myelodysplastic syndrome related to previous treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin with or without veliparib. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Up to 54 weeks

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

54 weeks

Every 9 weeks

Long-term Follow-up

Participants are monitored every 18 weeks until progression, and then every 6 months for up to 5 years.

Up to 5 years

Every 18 weeks until progression, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Veliparib

Trial Overview

The effectiveness of cisplatin chemotherapy with or without the addition of veliparib (a PARP inhibitor) is being tested in patients. The study aims to determine if preventing tumor cells from repairing DNA mutations using veliparib enhances treatment outcomes compared to cisplatin alone.

How Is the Trial Designed?

Group I: Arm II (cisplatin and veliparib) Experimental Treatment 3 Interventions

Patients receive cisplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-14. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (cisplatin and placebo) Active Control 3 Interventions

Patients receive cisplatin IV over 1 hour on day 1 and placebo PO BID on days 1-14. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36623515/

Cisplatin with veliparib or placebo in metastatic triple- ...

In the BRCA-like group, median progression-free survival was 5·9 months (95% CI 4·3-7·8) in the cisplatin plus veliparib group versus 4·2 months ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4911292/

Phase I Study of Veliparib (ABT-888) Combined with ...

Best overall response for 48 patients was radiologic response with 9-week confirmation for 17 (35%; 2 complete, 15 partial), and stable disease for 21 (44%).

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1470204522007392

Cisplatin with veliparib or placebo in metastatic triple ...

The addition of veliparib to cisplatin significantly improved progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer, but ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.1001

veliparib in metastatic triple-negative breast cancer (TNBC) ...

Conclusions: Addition of Vel to cisplatin significantly improved PFS and showed a trend towards improved OS for BRCA-like advanced TNBC.

5.

acsjournals.onlinelibrary.wiley.com

acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.31218

Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib ...

1A). No BRCA– patients had an objective tumor response. BRCA+ patients had a median overall survival of 23.3 months (95% CI, 3.8-30.2 months), ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9924094/

Cisplatin with veliparib or placebo in metastatic triple-negative ...

Veliparib is an oral small molecule inhibitor of PARP1 and PARP2 and has shown antitumor activity both as a single agent and in combination with platinum-based ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2949713225000965

Safety and efficacy of Cisplatin in combination with ...

Conclusion. The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01104259

Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating ...

This phase I trial studies the side effects and best dose of veliparib when given together with cisplatin and vinorelbine ditartrate in treating patients ...

9.

thelancet.com

thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00739-2/abstract

Cisplatin with veliparib or placebo in metastatic triple ...

In the BRCA-like group, median progression-free survival was 5·9 months (95% CI 4·3–7·8) in the cisplatin plus veliparib group versus 4·2 months ...