Carboplatin +/− Nivolumab for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two drugs, Carboplatin and Nivolumab (an immunotherapy drug), can more effectively treat triple-negative breast cancer that has spread. Participants will receive either Carboplatin alone or a combination of Carboplatin and Nivolumab to determine which is more effective. Suitable candidates for this trial have advanced or metastatic triple-negative breast cancer and have not received chemotherapy for their metastatic cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that combining Carboplatin with Nivolumab is under study for safety in treating metastatic breast cancer. Patients who previously took Nivolumab, an immune-boosting drug, with platinum-based drugs like Carboplatin have experienced various outcomes. Several studies have reported on the safety of this combination, but researchers continue to evaluate possible side effects.

Reports indicate that many patients tolerate the combination well. However, like any treatment, side effects can occur, such as tiredness, nausea, or more serious reactions. It is important to discuss potential risks with a doctor and consider all information before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Carboplatin and Nivolumab for breast cancer because it potentially offers a new way to enhance the immune system's ability to fight cancer. Unlike standard treatments that primarily target cancer cells directly, Nivolumab is an immunotherapy that works by blocking a protein called PD-1, which can help the immune system recognize and attack cancer cells more effectively. When combined with Carboplatin, a chemotherapy drug that damages the DNA of cancer cells, this approach may lead to a more comprehensive attack on the cancer. This combination could offer an innovative and potentially more effective option for patients, especially those who have exhausted other treatment avenues.

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

Research has shown that carboplatin, a chemotherapy drug, effectively treats certain cancers, including breast cancer. It damages the DNA in cancer cells, stopping their growth and spread. Nivolumab, an immunotherapy, helps the immune system identify and attack cancer cells. Studies with nivolumab have shown promising results in other cancers, such as lung cancer, where it improved survival rates when combined with chemotherapy. In this trial, some participants will receive carboplatin alone, while others will receive a combination of carboplatin and nivolumab. Researchers are exploring this combination because it may enhance treatment for triple-negative breast cancer that has spread. ^{1 2 5 6 7}

Who Is on the Research Team?

Sara M. Tolaney, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03414684

Carboplatin +/- Nivolumab in Metastatic Triple Negative ... The purpose of this research study is to determine how well carboplatin, by itself, or together with nivolumab, works in treating breast cancer that has spread ...

2. onclive.com onclive.com/view/neoadjuvant-nivolumab-plus-chemo-significantly-improves-os-vs-chemo-in-resectable-nsclc

Neoadjuvant Nivolumab Plus Chemo Significantly ... Neoadjuvant nivolumab plus chemotherapy significantly improved OS in resectable NSCLC, with a 28% reduction in death risk compared to ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601743/

Pharmacoeconomic Review - Nivolumab (Opdivo) - NCBI - NIH At a WTP of $50,000 per QALY, the probabilities of nivolumab being cost-effective was 0% compared to observation and 0% compared to adjuvant chemotherapy. At ...

4. fda.gov fda.gov/media/168489/download

NDA/BLA Multi-disciplinary Review and Evaluation OPDIVO, as a single agent or in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.66.9861

Nivolumab in Combination With Platinum‐Based Doublet ... PFS and OS ... The 24-week PFS rate ranged from 38% to 71% across arms, with median PFS time ranging from 4.8 to 7.1 months (Table 4, Fig 2A).

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/n/tr112990303/tr112990303_ch01_bp1/

Clinical Review - Nivolumab (Opdivo) - NCBI Bookshelf - NIH The objective of this CADTH report is to perform a systematic review of the beneficial and harmful effects of nivolumab (360 mg) in combination with platinum- ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/84/NCT03414684/Prot_SAP_000.pdf

DF/HCC Protocol #: 17-512 2.6.4 Safety of the Combination of Carboplatin and Nivolumab. The safety of the combination of nivolumab and carboplatin has only been reported with doublet.