Chemotherapy Combinations for Triple-Negative Breast Cancer

Not currently recruiting at 1322 trial locations

Overseen By Leon C. Hwang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must not be taking: Sex hormones, Corticosteroids

Disqualifiers: Metastatic disease, Cardiac disease, Hypertension, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different chemotherapy drug combinations for individuals with triple-negative breast cancer. Researchers are comparing two groups: one receives doxorubicin and cyclophosphamide followed by paclitaxel, while the other receives the same drugs plus carboplatin. Participants should have undergone surgery for triple-negative breast cancer that has not spread and have a HER2-negative tumor, which does not grow in response to a specific protein. As a Phase 3 trial, this study serves as the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require stopping sex hormonal therapy like birth control pills before joining. It's best to discuss your specific medications with the trial team.

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

Research has shown that treatments using doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel, are generally well-tolerated by breast cancer patients. These drugs effectively stop cancer cells from growing.

When used together, common side effects include hair loss, nausea, and tiredness. Serious side effects are less common but can include heart problems and lower blood cell counts, increasing the risk of infections. Adding carboplatin to this combination can enhance its effectiveness against cancer but may also increase side effects like low blood counts and nerve damage.

Extensive studies have evaluated these treatments, and despite some risks, they are considered safe enough for large clinical trials. This trial phase indicates that researchers have carefully assessed the treatment's safety, with many patients handling it well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for triple-negative breast cancer because they explore new chemotherapy combinations that could enhance effectiveness. Unlike the standard regimens, which typically involve sequential use of drugs like doxorubicin, cyclophosphamide, and paclitaxel, one arm of this trial adds carboplatin to the mix. This addition could potentially increase the treatment's ability to target and destroy cancer cells. By adjusting the combination and timing of these drugs, the treatments aim to improve patient outcomes and offer new hope for those battling this aggressive form of breast cancer.

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

Research has shown that a combination of three drugs—doxorubicin hydrochloride, cyclophosphamide, and paclitaxel—works well for treating triple-negative breast cancer. In this trial, participants in Arm I will receive this combination, which studies have found to be safe and effective in significantly shrinking tumors. Meanwhile, participants in Arm II will receive the same combination with the addition of carboplatin. Previous studies have shown that adding carboplatin can improve outcomes for some patients, increasing the chances of the cancer completely disappearing in more cases. These findings strongly support the potential effectiveness of these chemotherapy combinations in managing triple-negative breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Vicente Valero

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with triple-negative breast cancer who have good blood counts, no metastatic disease on imaging, and a performance status indicating they can care for themselves. They must not be pregnant or breastfeeding, haven't received certain cancer treatments before, and don't have other serious health issues that would interfere with the study.

Inclusion Criteria

My breast cancer has spread to nearby lymph nodes but not to distant parts of my body.

I have had a mastectomy or lumpectomy.

My kidneys are working well.

Exclusion Criteria

You have mental health or addiction issues that may interfere with the study requirements.

I have a lung condition that makes it hard for me to breathe.

My breast cancer is advanced (T4) or inflammatory.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel with or without carboplatin

20 weeks

Weekly visits for paclitaxel, every 2-3 weeks for other drugs

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 6 months for 5 years, then annually for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Paclitaxel

Trial Overview The trial is testing if adding carboplatin to a chemotherapy regimen of doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel improves outcomes in treating triple-negative breast cancer compared to the regimen without carboplatin.

How Is the Trial Designed?

Group I: Arm II (AC-->WP + carboplatin) Experimental Treatment 5 Interventions

Patients receive doxorubicin hydrochloride and cyclophosphamide as in Arm I. Patients then receive paclitaxel IV over 60 minutes on days 1, 8, and 15 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (AC-->WP) Active Control 4 Interventions

Patients receive doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel IV over 60 minutes on day 1. Treatment repeats weekly for 12 courses in the absence of disease progression or unacceptable toxicity.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

DZ-2384, a new microtubule-targeting agent, shows strong effectiveness against triple-negative breast cancer (TNBC) in preclinical models, outperforming traditional taxanes like paclitaxel in terms of reduced toxicity and a wider therapeutic window (14-32 compared to 2.0 for paclitaxel).

DZ-2384 not only effectively reduces brain metastatic lesions but also works synergistically with anti-CTLA-4 immunotherapy, suggesting it could enhance treatment outcomes when combined with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DZ-2384 has a superior preclinical profile to taxanes for the treatment of triple-negative breast cancer and is synergistic with anti-CTLA-4 immunotherapy. Bernier, C., Soliman, A., Gravel, M., et al.[2019]

Triple-negative breast cancer, which makes up 15%-20% of all breast cancers, has a high risk of relapse and death, highlighting the need for effective treatment strategies.

DNA alkylating agents like cisplatin have shown effectiveness in treating triple-negative breast cancer, especially when combined with targeted therapies such as PARP inhibitors, particularly for patients with BRCA1 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The triple-negative subtype: new ideas for the poorest prognosis breast cancer. Curigliano, G., Goldhirsch, A.[2022]

Currently, cytotoxic chemotherapy is the only proven systemic treatment for triple-negative breast cancer, which lacks key hormone receptors and HER2 overexpression.

The review highlights emerging management strategies, including targeted agents, biologics, and immunotherapy, that may significantly improve treatment options for triple-negative breast cancer in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Approach to Triple-Negative Breast Cancer. Gadi, VK., Davidson, NE.[2018]

Epirubicin, which has lower cardiotoxicity than doxorubicin, allows for higher cumulative doses and is effective in treating metastatic breast cancer, making it a safer option for patients.

A phase III trial is set to compare the effectiveness of a concurrent epirubicin/taxane regimen against a sequential epirubicin/cyclophosphamide followed by taxane treatment in patients with operable node-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of a phase III trial of adjuvant sequential epirubicin/ cyclophosphamide and taxane versus concurrent epirubicin/taxane in operable node-positive breast cancer. Perez, EA.[2019]

Triple negative breast cancer is highly aggressive, and while systemic chemotherapy has improved outcomes for early-stage patients, metastatic recurrences remain a significant concern.

Adding carboplatin to standard chemotherapy regimens enhances the likelihood of achieving a complete pathologic response, although it increases toxicity; additionally, adjuvant capecitabine has been shown to improve long-term outcomes for patients with residual disease after neoadjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early stage triple negative breast cancer: Management and future directions. Chaudhary, LN.[2021]

Paclitaxel (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

Triple-negative breast cancer is a diverse and aggressive type of cancer, and while molecular characterization isn't standard practice, it can help in understanding the disease better and predicting outcomes.

Recent advances in treatment options include neoadjuvant platinum-based chemotherapy and targeted therapies for patients with BRCA mutations, which may improve outcomes in various stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the systemic treatment of triple-negative breast cancer. Lebert, JM., Lester, R., Powell, E., et al.[2023]

In a meta-analysis of 14 studies involving 3518 early-stage triple negative breast cancer patients, the addition of platinum agents to chemotherapy significantly improved disease-free survival (DFS) but did not affect overall survival (OS).

While platinum-based treatment showed better DFS (HR 0.71), it was associated with increased toxicity, including higher rates of thrombocytopenia and neuropathy, indicating that its use should be carefully considered in unselected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis. Saleh, RR., Nadler, MB., Desnoyers, A., et al.[2021]

Citations

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