Carboplatin +/− Nivolumab for Breast Cancer

Recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Brain metastases, Autoimmune disease, HIV, 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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

78 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a drug called Carboplatin with or without another study drug, Nivolumab as a possible treatment for triple-negative breast cancer that has spread to other parts of the body. The interventions involved in this study are: * Carboplatin * Nivolumab

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 take other anti-cancer therapies during the study. You can continue using bisphosphonates or RANK ligand inhibitors if you are already on them.

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

Research shows that platinum drugs like Carboplatin are effective in aggressive breast cancers, especially when combined with other treatments. In particular, Carboplatin has been shown to increase response rates in certain types of breast cancer, such as those with BRCA mutations. ^{1 2 3 4 5}

Is the combination of Carboplatin and Nivolumab safe for humans?

Carboplatin, also known as Paraplatin, is generally considered safe with mild side effects like nausea and bone marrow suppression, but it should be used cautiously in people with kidney issues. Nivolumab, marketed as Opdivo, is an immunotherapy drug that has been used safely in various cancers, though it can cause immune-related side effects. While specific safety data for the combination of Carboplatin and Nivolumab in breast cancer is limited, both drugs have been used safely in other conditions. ^{2 3 6 7 8}

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

The combination of Carboplatin and Nivolumab is unique because it pairs a chemotherapy drug (Carboplatin) with an immunotherapy drug (Nivolumab), which may enhance the body's immune response against cancer cells. This approach is different from traditional chemotherapy alone and could offer a novel treatment option for breast cancer, especially in cases where other treatments have limited effectiveness. ^{2 3 6 9 10}

Research Team

Sara M. Tolaney, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for women over 18 with metastatic triple-negative breast cancer who haven't had chemotherapy for it yet. They must not be pregnant, have normal organ function, and no history of certain cancers or immune conditions. Participants need to agree to use contraception and can undergo a biopsy if needed.

Inclusion Criteria

I agree to a research biopsy if my tumor can be safely accessed.

I have not taken PARP inhibitors for metastatic cancer.

I am a woman who can have children and have a recent negative pregnancy test.

Exclusion Criteria

You have HIV, Hepatitis B, or Hepatitis C.

I have not had major surgery in the last 2 weeks.

I am allergic to platinum-based chemotherapy or nivolumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Carboplatin with or without Nivolumab every three weeks intravenously

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are assessed for progression-free survival and overall survival

up to 3.5 years

Treatment Details

Interventions

• Carboplatin
• Nivolumab

Trial Overview The study tests Carboplatin alone versus Carboplatin combined with Nivolumab in treating advanced breast cancer. It aims to see if adding Nivolumab improves outcomes. Patients will be assigned randomly to receive either the single drug or the combination therapy.

Participant Groups

Group I: Carboplatin + Nivolumab Experimental Treatment 2 Interventions

* Nivolumab is administered every three weeks intravenously * Nivolumab dosage is 360mg * Carboplatin is administered every three weeks intravenously * Carboplatin dosage is pre-determined by the PI

Group II: Carboplatin Active Control 1 Intervention

* Carboplatin is administered every three weeks intravenously * Carboplatin dosage is pre-determined by the PI

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Platinum analogs, such as carboplatin and cisplatin, show significant antitumor activity in aggressive breast cancer types, particularly in HER2-positive and BRCA1 mutation carriers, enhancing treatment effectiveness when combined with other therapies.

Neoadjuvant treatment with carboplatin increases the pathologic complete response (pCR) rates in both BRCA-mutated and sporadic triple-negative breast cancer, indicating its potential as a key component in chemotherapy regimens, although optimal dosing and scheduling still need to be clarified through ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the role of platinum agents in aggressive breast cancers. Sikov, WM.[2022]

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

In a phase II study involving 50 patients with locally advanced or metastatic breast cancer, the combination of pemetrexed and carboplatin showed a promising overall response rate of 54%, with a median response duration of 11.1 months.

The treatment was associated with manageable safety concerns, primarily hematologic toxicities, including grade 3/4 neutropenia in 58% of patients, but no severe non-hematologic toxicities were reported, indicating an acceptable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. Garin, A., Manikhas, A., Biakhov, M., et al.[2015]

Carboplatin (CBDCA) has shown similar effectiveness to cisplatin in treating various cancers, including head and neck and ovarian cancers, while demonstrating significantly lower toxicity, particularly in terms of renal effects and side effects like nausea and vomiting.

In clinical trials, carboplatin's dose-limiting factor was myelosuppression, making it a safer alternative to cisplatin, which has more severe side effects, thus positioning carboplatin as a valuable option in cancer chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of carboplatin]. Tsukagoshi, S.[2013]

A phase I trial involving 33 patients tested the combination of cisplatin and carboplatin, revealing that while the combination is feasible, it can lead to unexpectedly severe thrombocytopenia (low platelet count) when using specific doses, particularly 280 mg/m2 carboplatin with 25 mg/m2 cisplatin.

Despite the risk of thrombocytopenia, the combination therapy showed promising responses in tumors known to be responsive to platinum-based treatments, suggesting that further investigation into this combination is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. Trump, DL., Grem, JL., Tutsch, KD., et al.[2017]

In a study of 31 patients with recurrent or metastatic head and neck cancer, carboplatin showed a 26% response rate (complete or partial responses) with a median duration of 4.5 months, indicating its potential effectiveness against advanced squamous-cell carcinoma.

Carboplatin demonstrated a different toxicity profile compared to cisplatin, with moderate bone marrow suppression being the main side effect, while avoiding nephrotoxicity and allowing for outpatient treatment, making it a safer option for patients with renal concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. Eisenberger, M., Hornedo, J., Silva, H., et al.[2017]

References

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

Assessing the role of platinum agents in aggressive breast cancers. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. [2015]

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

Platinum containing regimens for metastatic breast cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Platinum containing regimens for metastatic breast cancer. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

[Development of carboplatin]. [2013]

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

Platinum analogue combination chemotherapy: cisplatin and carboplatin--a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. [2017]

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

Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. [2017]

9. Germany pubmed.ncbi.nlm.nih.gov

Carboplatin activity in untreated metastatic breast cancer patients--results of a phase II study. [2019]

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

Carboplatin in combination therapy for metastatic breast cancer. [2013]