Triple Drug Combo for Breast Cancer

Recruiting in Lee's Summit (>99 mi)

+6 other 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

51 Participants Needed

Trial Summary

What is the purpose of this trial?

Study combination use of cisplatin plus romidepsin and nivolumab in metastatic triple negative breast cancer (TNBC) or BRCA mutation-associated locally recurrent or metastatic breast cancer

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.

What data supports the effectiveness of the triple drug combo for breast cancer?

Cisplatin, a component of the triple drug combo, has shown effectiveness in treating triple-negative breast cancer (TNBC), especially in cases where other treatments have failed. Additionally, platinum-based therapies, which include cisplatin, have been effective in treating advanced and drug-resistant breast cancers, suggesting potential benefits for this combination treatment. ^{1 2 3 4 5}

What safety data exists for the drugs in the Triple Drug Combo for Breast Cancer?

Cisplatin, a key component of the treatment, has been used for over 40 years and is known to cause side effects like nausea, vomiting, and kidney issues, but these can often be managed with proper precautions. It has been tested extensively and is generally considered safe when used under medical supervision, though it can cause hearing loss and nerve damage in some cases. Second-generation analogs like carboplatin have been developed to reduce kidney toxicity, but they may cause more blood-related side effects. ^{4 6 7 8 9}

What makes the triple drug combo for breast cancer unique?

The triple drug combo for breast cancer is unique because it combines cisplatin, which is effective in certain breast cancers, with nivolumab, an immune system booster, and romidepsin, which modifies gene expression, potentially offering a novel approach by targeting cancer cells in multiple ways. ^{1 2 3 10 11}

Research Team

Priyanka Sharma, MD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

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

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

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

A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

In vitro interactions between platinum analogues in human ovarian-carcinoma cell lines. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

[Platinum-based chemotherapy in triple negative breast cancer]. [2013]

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

Current State of Platinum Complexes for the Treatment of Advanced and Drug-Resistant Breast Cancers. [2019]

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

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

7. England 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. [2019]

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

Clinical pharmacology and pharmacokinetics of cis-platinum and analogs. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. [2013]

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

Docetaxel/trastuzumab combination therapy for the treatment of breast cancer. [2019]

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

Platinum compounds in the treatment of advanced breast cancer. [2018]