Triple Drug Combo for Breast Cancer

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Priyanka Sharma

Must not be taking: CYP3A4 inhibitors, Corticosteroids

Disqualifiers: Pregnancy, HIV, Hepatitis, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—cisplatin, romidepsin, and nivolumab—to evaluate their effectiveness against advanced breast cancer. The focus is on metastatic triple negative breast cancer (TNBC) and breast cancer linked to BRCA mutations that have spread or returned locally. Individuals with TNBC or a BRCA mutation and a measurable tumor may be suitable candidates. The goal is to determine if these drugs can effectively treat these challenging types of breast cancer. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any anti-cancer therapy, including chemotherapy, immunotherapy, or biologic therapy, at least 14 days before starting the study drugs. Additionally, you must stop taking drugs that are moderate or strong inhibitors or inducers of the enzyme CYP3A, and you cannot be on warfarin or similar anticoagulants. Please consult with the trial team for specific guidance on your medications.

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

Research shows that the combination of romidepsin, cisplatin, and nivolumab is generally well-tolerated by patients with breast cancer. Studies have found this combination to be safe and effective, offering hope for those with advanced or recurrent breast cancer.

Reports indicate that the pairing of romidepsin and cisplatin has manageable side effects. Adding nivolumab appears to enhance the treatment's effectiveness while maintaining tolerability.

Although side effects can occur with any treatment, current evidence suggests that this combination is safe for people with breast cancer, making it a promising option for those considering participation in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this triple drug combo for breast cancer because it combines the powers of cisplatin, nivolumab, and romidepsin, each bringing a unique strength to the table. Unlike standard treatments like chemotherapy alone, this combo not only attacks cancer cells directly with cisplatin but also boosts the immune system with nivolumab, an immune checkpoint inhibitor. Romidepsin, a histone deacetylase inhibitor, adds another layer by modifying gene expression to potentially make cancer cells more sensitive to treatment. This multi-pronged approach is what sets it apart from existing treatments and gives researchers hope for more effective outcomes.

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

This trial will evaluate different combinations of romidepsin and cisplatin, with some participants also receiving nivolumab. Research has shown that a combination of romidepsin, cisplatin, and nivolumab may effectively treat certain aggressive breast cancers, such as metastatic triple-negative breast cancer (mTNBC) and breast cancer linked to BRCA mutations. Studies have found this combination to be safe and capable of reducing cancer cell growth and spread. Nivolumab, which helps the immune system fight cancer, plays a key role by overcoming resistance to cisplatin, a common issue in cancer treatment. Specifically, another study found that this drug combination significantly lowered the risk of cancer progression, offering a new potential treatment for patients with hard-to-treat breast cancers. Overall, these treatments provide hope for better outcomes in aggressive breast cancer types. ^{1 2 3 5 6}

Who Is on the Research Team?

Priyanka Sharma, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with triple negative breast cancer or BRCA mutation-associated breast cancer that's locally recurrent or metastatic. They must have had prior chemotherapy, be in a stable condition if they've had brain metastasis treatment, and not be pregnant. Those with certain health conditions, recent surgeries, active infections, or severe allergies are excluded.

Inclusion Criteria

I have triple-negative breast cancer or a confirmed BRCA1/2 mutation.

My breast cancer is at an advanced stage and cannot be cured with surgery or radiation.

I've had chemotherapy and, if applicable, hormonal therapy for my cancer.

Exclusion Criteria

I have had cancer within the last 3 years or have another cancer now.

I do not have any mental or physical health conditions that would make cancer treatment too risky for me.

I have tested positive for HIV/AIDS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the highest dose of romidepsin that is safe and tolerable in combination with cisplatin

6-12 weeks

3-4 visits (in-person) per cycle

Phase II Treatment

Evaluate the safety and effectiveness of romidepsin, cisplatin, and nivolumab combination

12-24 weeks

3-4 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Nivolumab
• Romidepsin

Trial Overview The study tests a combination of cisplatin (a chemotherapy drug), romidepsin (an anticancer agent), and nivolumab (an immunotherapy) on patients with advanced breast cancer to see how well it works compared to existing treatments.

How Is the Trial Designed?

Group I: Romidepsin Dose Expansion Experimental Treatment 3 Interventions

Romidepsin maximum tolerated dose (MTD) from Phase I IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle Nivolumab 360mg on day 1 of each 21 day cycle

Group II: Romidepsin (8mg/m2) + Cisplatin (75mg/m2) Experimental Treatment 2 Interventions

Romidepsin 8mg/m2 IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle

Group III: Romidepsin (12mg/m2) + Cisplatin (75mg/m2) Experimental Treatment 2 Interventions

Romidepsin 12mg/m2 IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle

Group IV: Romidepsin (10mg/m2) + Cisplatin (75mg/m2) Experimental Treatment 2 Interventions

Romidepsin 10mg/m2 IV on days 2 \& 9 of each 21 day cycle Cisplatin 75mg/m2 IV on day 1 of each 21 day cycle

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?

Priyanka Sharma

Lead Sponsor

Trials

4

Recruited

1,200+

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

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Published Research Related to This Trial

Trastuzumab effectively targets HER-2, a protein overexpressed in about 20% of breast cancers, and has shown clinical benefits when used alone or with chemotherapy, particularly in patients with HER-2 amplification.

Combining trastuzumab with docetaxel, a powerful chemotherapy drug, has demonstrated significant efficacy in treating HER-2-positive breast cancer, making these combinations some of the most effective therapies available for both metastatic and early-stage patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel/trastuzumab combination therapy for the treatment of breast cancer. Nabholtz, JM., Gligorov, J.[2019]

Cisplatin (CDDP) has been a key treatment for various cancers since 1972, but its use is limited by significant toxicities, particularly renal impairment.

Carboplatin (CBDCA), a second-generation analogue of cisplatin, has shown reduced renal toxicity and is effective against advanced cancers, although it can cause myelosuppression, particularly affecting platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. Ariyoshi, Y., Ota, K.[2013]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

Recent studies indicate that combining taxane, platinum, and trastuzumab is an effective first-line treatment for HER2-overexpressing metastatic breast cancer.

Docetaxel and carboplatin are also viable options for first-line treatment of HER2-negative metastatic breast cancer and for neoadjuvant therapy in locally advanced cases, suggesting a potential shift in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer: review of platinum-based cooperative group trials. Pegram, M.[2015]

Carboplatin, a platinum analogue of cisplatin, shows comparable antitumor activity against various cancers while significantly reducing renal and neurotoxic side effects, making it a safer alternative.

Preliminary studies on iproplatin indicate it may also have reduced renal and neurologic toxicity similar to carboplatin, with efficacy comparable to cisplatin, suggesting it could be another promising option in chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and II agents in cancer therapy: two cisplatin analogues and high-dose cisplatin in hypertonic saline or with thiosulfate protection. Fuks, JZ., Wadler, S., Wiernik, PH.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8489834/

A triple combination gemcitabine+romidepsin+cisplatin to ... Treatment with gemcitabine+romidepsin+cisplatin reduced the TNBC MDA-MB231 and MDA-MB468 cell survival to ~50% and ~15%, as well as invasiveness to ~31% and ~13 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02393794?term=platinum%20TNBC&viewType=Table&rank=10

Cisplatin Plus Romidepsin & Nivolumab in Locally ... Study combination use of cisplatin plus romidepsin and nivolumab ... cisplatin and nivolumab is safe and effective in treating patients with breast cancer.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.1076

Romidepsin (HDACi) plus cisplatin and nivolumab triplet ... Conclusions: The triplet combination of romidepsin plus cisplatin and nivolumab was well tolerated and shows encouraging efficacy in pretreated ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9031877/

Application of Approved Cisplatin Derivatives in Combination ... In advanced breast cancer, Trastuzumab in combination with Cisplatin, Carboplatin and Docetaxel has shown promising clinical activity. A very important strategy ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT331341

Romidepsin (HDACi) plus cisplatin and nivolumab triplet ... Conclusions: The triplet combination of romidepsin plus cisplatin and nivolumab was well tolerated and shows encouraging efficacy in pretreated mTNBC, ...

6. aetna.com aetna.com/cpb/medical/data/800_899/0865.html

Romidepsin - Medical Clinical Policy Bulletins Wang and associates (2017) stated that romidepsin (FK228) is one of the most promising HDAC inhibitors due to its potent anti-tumor activity, and has been used ...