Chemotherapy for Breast Cancer

Recruiting at 495 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Heart failure, Hypertension, 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: Unknown

454 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on warfarin, you must have a stable dose with an INR of 3 or less and no active bleeding.

Is chemotherapy for breast cancer generally safe for humans?

Chemotherapy treatments like doxorubicin and paclitaxel have been studied for safety, with some reports of cardiac (heart-related) side effects, especially when used together. However, limiting the dose of doxorubicin can help manage these risks, and ongoing studies are exploring ways to reduce cardiac toxicity further. Other side effects of paclitaxel include allergic reactions, low white blood cell counts, nerve damage, and hair loss. ^{1 2 3 4 5}

How is the chemotherapy drug combination of Cyclophosphamide, Doxorubicin Hydrochloride, and Paclitaxel unique for breast cancer treatment?

This chemotherapy drug combination is unique because it uses both anthracyclines (like Doxorubicin) and taxanes (like Paclitaxel) in a sequential regimen, which is a common and effective approach for reducing cancer recurrence in breast cancer patients. The combination is well-established for its safety and efficacy, providing a balance between effectiveness and manageable side effects. ^{6 7 8 9 10}

What evidence supports the effectiveness of the drug combination used in the chemotherapy for breast cancer trial?

Research shows that combining paclitaxel and doxorubicin is highly effective in treating advanced breast cancer, with manageable side effects. Additionally, Abraxane and cyclophosphamide have shown better outcomes in recurrent breast cancer compared to other therapies, suggesting the potential effectiveness of this drug combination. ^{11 12 13 14 15}

Who Is on the Research Team?

William M Sikov

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for patients with breast cancer that can be surgically removed. They must have hormone receptor-poor tumors, no significant bleeding or heart issues in the past 6 months, and normal organ function tests. Pregnant women are excluded, as are those who've had prior treatments for this cancer. Participants need to agree to biopsies and use non-hormonal contraception if applicable.

Inclusion Criteria

Patient agrees to undergo pretreatment research biopsies

My breast tumor is at least 1 cm big, or I have measurable axillary adenopathy.

Your kidney function is too high, with a filtration rate of more than 30 milliliters per minute.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive paclitaxel weekly for 12 weeks, followed by dose-dense doxorubicin and cyclophosphamide every 2 weeks for 4 cycles

19 weeks

Weekly visits for paclitaxel, bi-weekly visits for ddAC

Surgery

Definitive surgery, either modified radical mastectomy or breast-conserving surgery, is performed 4-8 weeks after completion of neoadjuvant therapy

4-8 weeks

Follow-up

Participants are monitored for safety, effectiveness, and recurrence-free survival

up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Paclitaxel

Trial Overview The study is testing how well paclitaxel works alone or combined with carboplatin and/or bevacizumab before surgery, followed by doxorubicin and cyclophosphamide. It aims to see if adding these drugs makes the tumor smaller compared to standard chemotherapy alone.

How Is the Trial Designed?

Group I: Arm IV (paclitaxel, ddAC, bevacizumab, carboplatin) Experimental Treatment 6 Interventions

Patients receive paclitaxel and ddAC as in Arm I, bevacizumab as in Arm II, and carboplatin as in Arm III.

Group II: Arm III (paclitaxel, ddAC, carboplatin) Experimental Treatment 5 Interventions

Patients receive paclitaxel and ddAC as in Arm I. Patients also receive carboplatin IV over 30 minutes once in weeks 1, 4, 7, and 10.

Group III: Arm II (paclitaxel, ddAC, bevacizumab) Experimental Treatment 5 Interventions

Patients receive paclitaxel and ddAC as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes in weeks 1, 3, 5, 7, 9, 11, 13, 15, and 17.

Group IV: Arm I (paclitaxel, doxorubicin, cyclophosphamide) Active Control 4 Interventions

Patients receive paclitaxel IV over 60 minutes once weekly in weeks 1-12. Patients then receive dose-dense doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 5-30 minutes (ddAC) once in weeks 13, 15, 17, and 19.

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+

Published Research Related to This Trial

Paclitaxel has shown high effectiveness in treating advanced breast cancer, including cases resistant to anthracyclines, prompting research into its combination with anthracyclines like doxorubicin.

Clinical trials of the paclitaxel/doxorubicin combination have reported promising response rates, although the toxicity profiles vary significantly based on the administration schedule used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and doxorubicin in metastatic breast cancer. Gehl, J., Boesgaard, M., Paaske, T., et al.[2015]

A randomized trial by the Eastern Cooperative Oncology Group (ECOG) is comparing the effectiveness of single-agent doxorubicin, single-agent paclitaxel, and their combination in treating metastatic breast cancer, with initial results currently being analyzed.

ECOG is also exploring ways to reduce the cardiac toxicity associated with doxorubicin by adding dexrazoxane, while ongoing trials are investigating the combination of carboplatin and paclitaxel to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel doublets in metastatic breast cancer: Eastern Cooperative Oncology Group and Hoosier Oncology Group Studies. Sledge, GW.[2015]

In a study involving 2,305 women with primary breast cancer, intensifying the dose of cyclophosphamide in combination with doxorubicin did not lead to significant improvements in disease-free survival (DFS) or overall survival after 5 years.

Increasing the total dose of cyclophosphamide resulted in higher grade 4 toxicity, indicating that such intensification may not be safe or beneficial for patients outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. Fisher, B., Anderson, S., Wickerham, DL., et al.[2017]

The combination of intravenous paclitaxel and bolus doxorubicin is an effective primary chemotherapy for stage IV breast cancer, showing significant activity with manageable side effects.

Limiting the total dose of doxorubicin to 360 mg/m2 and using granulocyte colony-stimulating factor can reduce the risk of cardiotoxicity and neutropenia, while continuing treatment with paclitaxel can enhance the chances of a complete response in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience at the Istituto Nazionale Tumori with paclitaxel in combination with doxorubicin in women with untreated breast cancer. Gianni, L., Capri, G.[2015]

In a study of 47 elderly women with high-risk breast cancer, the combination of Non-Pegylated Liposomal Doxorubicin (NPL-DOX) and Cyclophosphamide followed by weekly Paclitaxel showed a low rate of cardiac toxicity over a median follow-up of 76 months, with only one case of grade 3 congestive heart failure reported.

While there was a gradual decline in left ventricular ejection fraction (LVEF) over time, it remained above 50% and did not lead to any significant clinical symptoms, indicating that the treatment is relatively safe for cardiac health in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study. Coltelli, L., Finale, C., Musettini, G., et al.[2023]

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]

Capecitabine alone was associated with a significantly higher incidence of nausea and vomiting compared to doxorubicin + paclitaxel, doxorubicin alone, and paclitaxel alone in patients with metastatic/advanced breast cancer, indicating it may be less tolerable for patients.

The doxorubicin + cyclophosphamide regimen showed a lower incidence of febrile neutropenia compared to the doxorubicin + docetaxel regimen, suggesting it may be a safer option regarding this specific toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer. Zhang, XH., Hao, S., Gao, B., et al.[2018]

The ASTER study demonstrated that a 6-month perioperative chemotherapy regimen combining Doxorubicin and Paclitaxel followed by Cyclophosphamide, Methotrexate, and 5-Fluorouracil is safe and effective for breast cancer treatment, with a low incidence of severe toxicities (8.5% grade III-IV hematologic toxicity).

With a follow-up of 6.7 years, the study reported high disease-free survival rates (99.6% at 1 year, 97.1% at 5 years) and overall survival rates (99.6% at 1 year, 94.9% at 5 years), indicating that this chemotherapy regimen is comparable in efficacy to other standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study. Mariani, G., Galli, G., Cavalieri, S., et al.[2019]

The TEC regimen, which includes docetaxel, epirubicin, and cyclophosphamide, demonstrated a pathologic complete response rate of 25% in a phase II study involving 20 patients with locally advanced breast cancer.

The treatment was well-tolerated, with a 5-year overall survival rate of 94.7% and no cases of cardiac failure or treatment-related deaths, although neutropenia was a common side effect in 35% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer. Yao, X., Hosenpud, J., Chitambar, CR., et al.[2021]

Docetaxel, particularly in combination with doxorubicin and cyclophosphamide (the TAC regimen), has been established as an effective treatment for node-positive breast cancer, demonstrating significant efficacy in both metastatic and adjuvant settings.

While the TAC regimen is associated with higher toxicity compared to traditional treatments, the side effects can be managed effectively with colony-stimulating growth factor support, making it a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, doxorubicin and cyclophosphamide (the TAC regimen): an effective adjuvant treatment for operable breast cancer. Martin, M.[2016]

Citations

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

The efficacy and safety of preoperative chemotherapy with triweekly abraxane and cyclophosphamide followed by 5-Fluorouracil, epirubicin, and cyclophosphamide therapy for resectable breast cancer: a multicenter clinical trial. [2015]

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

Paclitaxel and doxorubicin in metastatic breast cancer. [2015]

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

Paclitaxel doublets in metastatic breast cancer: Eastern Cooperative Oncology Group and Hoosier Oncology Group Studies. [2015]

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

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. [2017]

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

Experience at the Istituto Nazionale Tumori with paclitaxel in combination with doxorubicin in women with untreated breast cancer. [2015]

6. Italy pubmed.ncbi.nlm.nih.gov

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study. [2023]

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

Combination chemotherapy with paclitaxel and doxorubicin for metastatic breast cancer. [2015]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Prospective assessment of cardiac toxicity during a randomized phase II trial of doxorubicin and paclitaxel in metastatic breast cancer. [2015]

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

A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Cognitive impairment and elevated peripheral cytokines in breast cancer patients receiving chemotherapy. [2023]

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

Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Sequencing of anthracyclines and taxanes in neoadjuvant and adjuvant therapy for early breast cancer. [2022]

14. Australia pubmed.ncbi.nlm.nih.gov

A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer. [2021]

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

Docetaxel, doxorubicin and cyclophosphamide (the TAC regimen): an effective adjuvant treatment for operable breast cancer. [2016]