Chemotherapy for Breast Cancer

Recruiting at 541 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: SWOG Cancer Research Network

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: 6

Duration: 24-30 weeks

3294 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating resected breast cancer. PURPOSE: This randomized phase III trial is comparing 2 different regimens of combination chemotherapy to see how well they work in treating patients who have undergone surgery for stage I, stage II, or stage III breast cancer.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that no prior chemotherapy for this breast cancer is allowed, so you may need to discuss your current treatments with the trial team.

What data 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, and cyclophosphamide combined with taxane enhances the antitumor effect. These combinations have shown promising results in improving outcomes for breast cancer patients. ^{1 2 3 4 5}

Is chemotherapy for breast cancer using drugs like Cyclophosphamide, Doxorubicin, and Paclitaxel generally safe for humans?

Research shows that while these drugs are effective against breast cancer, they can have side effects like cardiac toxicity (heart-related issues), neutropenia (low white blood cell count), and hypersensitivity reactions. However, studies have found ways to manage these risks, such as limiting doses and using protective agents, making the treatment generally safe with careful monitoring. ^{6 7 8 9 10}

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 and taxanes, which are effective in reducing cancer recurrence when used sequentially. The combination of these drugs is well-established for both neoadjuvant (before surgery) and adjuvant (after surgery) settings, providing a comprehensive approach to treating breast cancer. ^{11 12 13 14 15}

Research Team

Halle C Moore, MD

Principal Investigator

The Cleveland Clinic

George Thomas Budd, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for patients who've had surgery for stage I-III breast cancer. Eligible participants must have operable disease with no T4 tumors, high-risk features based on tumor size and nodal status, and known hormone receptor status. HER2/neu-positive tumors are allowed. Those with HIV, prior malignancy within 5 years (except certain skin or in situ cancers), or previous chemotherapy with specific drugs cannot join.

Inclusion Criteria

I have had surgery to remove breast cancer and affected lymph nodes.

My cancer is at an early or mid-stage and can be operated on.

I know my cancer's estrogen and progesterone receptor status.

Exclusion Criteria

My tumor is not HER2 positive.

I haven't had cancer in the past 5 years, except for certain skin cancers or early-stage cervical or breast cancer.

My tumor is smaller than 1 cm and doesn't meet certain criteria.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxorubicin, cyclophosphamide, and paclitaxel in various regimens as adjuvant therapy for breast cancer

24-30 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 6 months

Long-term follow-up

Participants are monitored annually for up to 15 years

10 years

Annually

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Paclitaxel

Trial Overview The study compares two post-surgery chemo regimens using doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see which is more effective against resected breast cancer. It's a phase III trial where patients are randomly assigned to one of the two drug combinations.

Participant Groups

Group I: Arm VI Experimental Treatment 5 Interventions

Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim as in arm V. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.

Group II: Arm V Experimental Treatment 5 Interventions

Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.

Group III: Arm IV Experimental Treatment 5 Interventions

(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.

Group IV: Arm II Experimental Treatment 5 Interventions

(closed 11/10/10) Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and G-CSF SC on days 2-7. Treatment repeats every 7 days for 15 courses. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel and pegfilgrastim as in arm I.

Group V: Arm I Active Control 5 Interventions

(closed 11/10/10) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 2 or filgrastim (G-CSF) SC on days 3-10. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.

Group VI: Arm III Active Control 5 Interventions

(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.

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?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. 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]

2. 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]

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

Paclitaxel and doxorubicin in metastatic breast cancer. [2015]

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

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

5. 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]

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

Treatment of metastatic breast cancer with combination paclitaxel/cyclophosphamide. [2015]

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

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

12. 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]

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

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

14. England pubmed.ncbi.nlm.nih.gov

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

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

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