Veliparib + Carboplatin for Breast Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Protease inhibitors

Disqualifiers: Active infection, Heart failure, Seizures, others

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

Compensation: Varies

Number of Visits: 21

Duration: 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and examine the side effects of combining veliparib with carboplatin for treating HER2-negative breast cancer that has spread. Carboplatin, a chemotherapy drug, damages the DNA of cancer cells, while veliparib prevents the cells from repairing this damage, potentially enhancing treatment effectiveness. The trial seeks participants with HER2-negative breast cancer that is either triple-negative or has specific genetic markers. Eligible participants should have received no more than three prior chemotherapy treatments for metastatic disease and must be able to swallow pills. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy or radiotherapy within 4 weeks before starting the study. You also cannot be on any other investigational drugs.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that patients generally tolerate the combination of veliparib and carboplatin well. Previous studies found that adding veliparib to carboplatin did not increase side effects compared to using carboplatin alone. Most side effects were manageable, meaning they were usually not severe and could be controlled. It's important to remember that this trial is in the early stages, so researchers are still learning about the treatment's safety. However, existing studies suggest that the treatment is generally safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of veliparib and carboplatin for breast cancer because it targets cancer cells in a unique way. Veliparib is a PARP inhibitor, which means it disrupts the repair process of DNA in cancer cells, making it harder for them to survive and multiply. Unlike standard chemotherapy treatments that attack all rapidly dividing cells, this approach is more precise, potentially leading to fewer side effects. Additionally, the use of carboplatin is well-established in cancer treatment, but when paired with veliparib, it may enhance the overall effectiveness against cancer cells. This combination could offer a more targeted and effective treatment option for patients.

What evidence suggests that veliparib and carboplatin might be an effective treatment for HER2-negative breast cancer?

Research has shown that using veliparib with carboplatin, the combination studied in this trial, may effectively treat HER2-negative breast cancer. Studies have found that adding carboplatin can increase the likelihood of complete tumor disappearance and improve long-term survival without cancer-related events. This combination has been particularly beneficial for patients with triple-negative breast cancer, demonstrating better survival rates without cancer progression over two and three years. Veliparib works by preventing cancer cells from repairing their DNA, increasing their sensitivity to carboplatin. Overall, this combination has shown promise with a manageable safety profile. ^{1 2 6 7 8}

Who Is on the Research Team?

Kai Johnson, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with HER2-negative metastatic breast cancer, particularly those whose tumors lack a certain repair pathway (FA deficiency) or have a BRCA1/2 mutation. Participants can have had up to three prior chemo treatments but must be four weeks out from the last one. They should be in relatively good health (ECOG <= 2), may have treated brain metastases, and meet specific blood cell count criteria.

Inclusion Criteria

My cancer is ER/PR positive, HER2 negative, and lacks the FA pathway.

My cancer is HER negative and I have a BRCA1/2 gene mutation.

Absolute neutrophil count >= 1,500/mcL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive carboplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21-day cycles

Visits every 21 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Periodic visits for monitoring

Long-term monitoring

Participants are monitored for long-term outcomes and biomarker analysis

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Veliparib

Trial Overview The study is testing the combination of Veliparib, which might stop tumor cells from repairing DNA damage, with Carboplatin, a chemotherapy drug that damages cancer cell DNA. The goal is to see if this combo works better than Carboplatin alone at killing tumor cells in patients with advanced breast cancer.

How Is the Trial Designed?

Group I: Treatment (veliparib, F 18 fluorothymidine, carboplatin) Experimental Treatment 6 Interventions

Patients receive carboplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo fluorothymidine PET scan and peripheral blood cell and tumor tissue collection periodically for correlative studies.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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/35093516/

Long-term efficacy and safety of addition of carboplatin with ... Conclusions: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34917174/

Safety and efficacy of veliparib plus carboplatin/paclitaxel ... Benefit was durable, with improved PFS rates at 2 years (HR+, 27.5% vs 15.3%; TNBC, 40.4% vs 25.0%) and 3 years (HR+, 17.5% vs 8.6%; TNBC, 35.3% vs 13.0%) in ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00018-7/fulltext

Long-term efficacy and safety of addition of carboplatin with ... Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.520

Phase 3 study evaluating efficacy and safety of veliparib (V ... Conclusions: Addition of V to neoadjuvant Cb + P followed by AC did not increase pCR rate in breast and nodes in stage II–III TNBC, while ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1513749

Adaptive Randomization of Veliparib–Carboplatin ... In summary, patients with triple-negative breast cancer in our trial were found to benefit from veliparib–carboplatin, whereas patients with ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0923753422000187

Long-term efficacy and safety of addition of carboplatin with ... Adding veliparib to carboplatin-containing neoadjuvant chemotherapy did not impact long-term outcomes in TNBC. •. Patients with pathological complete response ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02032277

NCT02032277 | A Study Evaluating Safety and Efficacy of ... This is a 3 arm Phase 3 study to evaluate the safety and efficacy of the addition of veliparib plus carboplatin versus the addition of carboplatin to standard ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT186952

Phase 3 study evaluating efficacy and safety of veliparib (V ... Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in ...