Veliparib + Carboplatin for Breast Cancer

Recruiting at 2 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

44 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Veliparib and Carboplatin for breast cancer?

Research shows that adding Veliparib to Carboplatin improves progression-free survival (the time during which the cancer does not get worse) in patients with certain types of breast cancer, such as those with BRCA mutations. Additionally, studies have found that this combination can lead to complete responses in some patients, meaning the cancer is no longer detectable. ^{1 2 3 4 5}

Is the combination of Veliparib and Carboplatin safe for humans?

The combination of Veliparib and Carboplatin has been studied in patients with advanced breast cancer, showing some side effects like nausea, dehydration, and low platelet counts (thrombocytopenia). However, the overall safety and effectiveness are considered encouraging, with some patients experiencing long-lasting positive responses. ^{1 2 5 6 7}

What makes the drug combination of Veliparib and Carboplatin unique for breast cancer treatment?

The combination of Veliparib, a PARP inhibitor (a drug that blocks an enzyme used by cancer cells to repair damage), with Carboplatin, a chemotherapy drug, is unique because it specifically targets breast cancer associated with BRCA gene mutations, potentially improving progression-free survival in patients with advanced or metastatic breast cancer. ^{1 2 4 5 6}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of veliparib when given together with carboplatin and to see how well they work in treating patients with human epidermal growth factor 2 (HER2)-negative breast cancer that has spread to other parts of the body. Carboplatin kills cancer cells by damaging the deoxyribonucleic acid (DNA) that lets the cancer cell survive and reproduce. The body has proteins that try to repair the damaged DNA. Veliparib may prevent these proteins from repairing the DNA so that carboplatin may be able to kill more tumor cells. Giving veliparib with carboplatin may kill more tumor cells than carboplatin alone.

Research Team

Kai Johnson, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line veliparib and carboplatin-paclitaxel in patients with HER2- advanced germline BRCA+ breast cancer: Subgroup analysis of a randomised clinical trial. [2021]

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

Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with Germline BRCA1- or BRCA2-Associated Metastatic Breast Cancer: California Cancer Consortium Trial NCT01149083. [2022]

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

A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of veliparib plus carboplatin/paclitaxel in patients with HER2-negative metastatic or locally advanced breast cancer: subgroup analyses by germline BRCA1/2 mutations and hormone receptor status from the phase-3 BROCADE3 trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study. [2023]