Chemotherapy + Trastuzumab for Breast Cancer

No longer recruiting at 1448 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anthracyclines, Taxanes, Trastuzumab, others

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: 9

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding trastuzumab, a drug that blocks cancer growth, to regular chemotherapy after surgery improves treatment for invasive breast cancer. Chemotherapy kills cancer cells, while trastuzumab specifically targets and blocks certain cancer cell functions. Participants will receive different combinations of these treatments to compare outcomes. Women who have had surgery for invasive breast cancer and have tumors that are HER2-low may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial requires that you stop taking certain medications, such as endocrine therapy (like tamoxifen) and sex hormonal therapy (like birth control pills), before joining. If you are on these medications, you must discontinue them prior to randomization.

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

Research shows that the combination of docetaxel, cyclophosphamide, and trastuzumab is generally easy for most people to handle. Studies have focused on how this combination might affect the heart, and results suggest it is safe for most patients, though some might experience heart-related issues, a known risk with trastuzumab.

For the combination of doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, research indicates it is usually well-tolerated. However, like the other treatment, there is a small risk of heart problems. These side effects are rare but important to monitor.

Earlier trials have studied both treatment combinations, and their safety is well-documented. These treatments are widely used and have been shown to be safe for most patients. However, participants should be aware of potential heart-related side effects and discuss any concerns with their healthcare team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining chemotherapy with trastuzumab for breast cancer because trastuzumab specifically targets the HER2 protein, which is overexpressed in some breast cancers. This targeted approach can enhance the effectiveness of chemotherapy drugs like cyclophosphamide, docetaxel, doxorubicin, and paclitaxel by directly attacking cancer cells that overexpress HER2, potentially leading to better outcomes. Unlike standard treatments that may not differentiate between cancerous and healthy cells, trastuzumab's targeted action reduces collateral damage to healthy cells, offering a more precise treatment option. This combination could improve survival rates and reduce side effects compared to traditional chemotherapy alone, making it a promising advance for patients with HER2-positive breast cancer.

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

Research shows that combining chemotherapy with trastuzumab holds promise for treating breast cancer. In this trial, participants in Arm II will receive trastuzumab alongside chemotherapy. Studies have found that adding trastuzumab to docetaxel and cyclophosphamide helps patients remain cancer-free longer after treatment. One study found that 85% of women completed a full year of trastuzumab treatment, indicating it is generally well-tolerated.

For the combination of doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, also part of Arm II in this trial, research suggests this mix improves outcomes for women with HER2-positive breast cancer. This type of cancer has an excess of the HER2 protein, which can accelerate growth. Adding trastuzumab has been linked to better survival rates. Overall, these treatments show encouraging results in helping patients live longer without cancer returning. ^{6 7 8 9 10}

Who Is on the Research Team?

Louis Fehrenbacher

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for women with invasive breast cancer who've had surgery. They must have a life expectancy of at least 10 years, not counting their cancer, and be in good health otherwise. Participants need proper organ function and no history of certain cancers or treatments within the last 5 years. Women must agree to avoid pregnancy during and after the trial for specified periods.

Inclusion Criteria

Your kidney function test within 6 weeks before the study must be within the normal range.

You have signed a consent form that has been approved by a review board and follows the rules set by the government and institution.

My cancer's HER2 status has been checked.

Exclusion Criteria

I have had breast cancer in both breasts at the same time or at different times.

I am currently on hormone therapy for my cancer.

Use of any investigational product within 30 days prior to randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy with or without trastuzumab. Chemotherapy regimens include docetaxel and cyclophosphamide or doxorubicin hydrochloride, cyclophosphamide, and paclitaxel. Trastuzumab is administered in some groups.

1 year

Every 3 weeks for chemotherapy, weekly for paclitaxel, and every 3 weeks for trastuzumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

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

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Docetaxel
• Doxorubicin
• Paclitaxel
• Trastuzumab

Trial Overview

The study compares chemotherapy alone versus chemotherapy with trastuzumab (a monoclonal antibody) post-surgery in treating breast cancer. It aims to determine if adding trastuzumab improves outcomes by preventing tumor growth or spread more effectively than chemotherapy alone.

How Is the Trial Designed?

Group I: Arm II (chemotherapy, trastuzumab) Experimental Treatment 8 Interventions

GROUP IIA: Patients receive docetaxel and cyclophosphamide as in Group IA. Patients also receive trastuzumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. GROUP IIB: Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in Group IB. Patients also receive trastuzumab IV over 30-90 minutes weekly for 12 doses and then every 3 weeks for subsequent doses. Treatment repeats every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (chemotherapy) Active Control 7 Interventions

GROUP IA: Patients receive docetaxel IV over 60 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. GROUP IB: Patients receive doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-3 weeks after last dose of doxorubicin hydrochloride and cyclophosphamide, patients also receive paclitaxel IV over 60 minutes once weekly for 12 doses 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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

A new regimen combining doxorubicin and paclitaxel has been developed that is both well-tolerated and highly effective, utilizing bolus administration of doxorubicin and a 3-hour infusion of paclitaxel, overcoming previous schedule-dependent toxicity issues.

Paclitaxel has shown promising results when combined with fluorouracil and folinic acid in patients with extensive prior chemotherapy, and adding mitoxantrone to this combination appears to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-based combination chemotherapy for breast cancer. Hortobagyi, GN.[2015]

Doxorubicin combined with docetaxel has shown high effectiveness in treating advanced breast cancer without significantly increasing the risk of congestive heart failure, unlike the combination with paclitaxel.

While the combination of doxorubicin and paclitaxel improved response rates, it did not enhance overall survival, highlighting the need for further evaluation of doxorubicin/docetaxel combinations in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compilation of phase I and II trial data of docetaxel and doxorubicin in the treatment of advanced breast cancer and other malignancies. Sparano, JA.[2018]

The combination of doxorubicin (Dox) and paclitaxel has been established as a superior treatment for metastatic breast cancer, showing better response rates and longer time to disease progression compared to either drug alone, based on a phase III study.

New agents like Herceptin (trastuzumab) and DPPE are being investigated to enhance the efficacy of Dox and paclitaxel, with early results indicating they may improve response rates and prolong disease progression time when used in combination with these chemotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in chemotherapy of advanced breast cancer. Lebwohl, DE., Canetta, R.[2016]

The combination of docetaxel and doxorubicin (TAC) has shown significantly higher response rates in advanced breast cancer treatment compared to traditional regimens, with a response rate of 54% versus 42% for the 5-fluorouracil/doxorubicin/cyclophosphamide regimen, based on a study involving 484 patients.

While TAC treatment was associated with a higher incidence of febrile neutropenia, it did not increase the risk of serious infections or cardiotoxicity, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the treatment of breast cancer: an update on recent studies. Nabholtz, JM., Reese, DM., Lindsay, MA., et al.[2019]

Docetaxel and doxorubicin combinations (TA or TAC) show high efficacy in treating metastatic breast cancer, with response rates between 70% to 80%, even in patients with visceral metastases.

The main toxicity observed is neutropenia, but significant cardiotoxicity has not been reported, even at high cumulative doses of doxorubicin, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer. Nabholtz, JM., Smylie, M., Mackey, J., et al.[2018]

The combination of docetaxel, doxorubicin, and cyclophosphamide (TAC) shows high efficacy in treating metastatic breast cancer, with response rates reaching up to 80% in preliminary phase II trials.

The TAC regimen is well tolerated, with low rates of cardiac toxicity (only 2% experienced reversible congestive heart failure) despite the high incidence of grade 4 neutropenia in 68% of treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel/doxorubicin/cyclophosphamide in the treatment of metastatic breast cancer. Nabholtz, JM., Smylie, M., Mackey, JR., et al.[2018]

Doxorubicin has historically been the most effective treatment for metastatic breast cancer, especially when combined with other agents like 5-fluorouracil and cyclophosphamide, leading to improved patient outcomes.

New agents such as docetaxel have shown significantly higher response rates than doxorubicin in phase III trials, and importantly, docetaxel does not carry the same risk of cardiotoxicity, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining new agents with anthracyclines in metastatic breast cancer: an overview of recent findings. Aapro, MS.[2018]

In a review of five phase III clinical trials, docetaxel was associated with a higher incidence of grade 3/4 neutropenia compared to paclitaxel, indicating a distinct safety profile for each taxane.

Paclitaxel was more likely to cause peripheral neuropathy, while docetaxel had higher rates of gastrointestinal adverse events, suggesting that the choice of taxane may depend on the patient's tolerance to these specific side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systemic review of taxanes and their side effects in metastatic breast cancer. Lai, JI., Chao, TC., Liu, CY., et al.[2022]

The doxorubicin-docetaxel combination is an effective first-line chemotherapy for metastatic breast cancer, achieving an overall response rate of 67% among 40 assessable patients, with 16% achieving complete remission and 51% partial remission.

The treatment was well-tolerated, with no severe cardiac or neurological toxicity reported, although 58% of patients experienced significant neutropenia, which was managed with G-CSF or GM-CSF support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial. Mattioli, R., Lippe, P., Massacesi, C., et al.[2018]

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