A Trial of Doxorubicin/Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D for Metastatic Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer; Neoplasm Metastasis

• Registration Number: NCT00190489
• Lead Sponsor: Japan Clinical Oncology Group

Brief Summary

To investigate the clinical benefits of Docetaxel or alternating AC-Docetaxel in comparison with standard AC for metastatic breast cancer

Detailed Description

power to detect a 50% increase in median TTF at 0.025 one-sided alpha in AC vs. D and AC vs. AC-D.

Results: 441pts (146 in AC, 147 in D, 148 in AC-D) were randomized between 01/99 and 05/03. Major grade 3-4 toxicities were neutropenia (26/45/46% for AC/D/AC-D), febrile neutropenia (3/4/6%), nausea/vomiting (3/3/4%). There was no toxic death. One grade 4 diarrhea in AC-D and 1 secondary leukemia (APL) in D were reported. Response (CR/PR) rates were 30, 41, and 35% for AC, D, and AC-D respectively. Median TTF (AC, D, and AC-D) are 6.4, 6.4, and 6.7 months (p =.255 for AC vs. D, p =.275 for AC vs. AC-D), and median overall survival are 22.4, 25.7, and 25.0 months (p=.092 for AC vs. D, p=.076 for AC vs. AC-D). The same difference was shown by the adjusted Cox model.

Conclusions: No benefit was demonstrated in D and AC-D over AC in TTF, however, D and AC-D tended to be superior to AC in response rate and overall survival. Survival benefit of front-line docetaxel should be re-evaluated by further long follow-up.

Study Timeline

• Study Start: 1999-01
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-19
• Primary Completion: 2006-05
• Study Completion: 2006-05
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-31
• Last Update Posted: 2016-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 450

Inclusion Criteria

1. Hormonal therapy-resistant MBC
2. ER (-), failure of hormonal therapy for MBC, or relapse within 6 months after adjuvant hormonal therapy
3. No anthracyclines for MBC and no prior taxanes
4. At least 6 months from the completion of adjuvant chemotherapy
5. Measurable or evaluable lesions
6. Age: 20 to 75 years
7. PS: 0-3
8. WBC >= 4,000 /mm3 or ANC >=1,000 /mm3, Platelet >= 100,000 /mm3, SGOT/SGPT <= 1.5 x ULN, T-Bil <= 1.5 mg/dL, Cr <= 1.5 mg/dL
9. normal ECG
10. Written informed consent

Exclusion Criteria

1. pregnant
2. malignant pleural effusion, ascites, or pericardial effusion that requires emergent treatment
3. Active infection
4. other cancer present within the last 5 years
5. previous stem cell transplantation
6. brain metastasis that requires emergent treatment
7. relapse within 6 months after completion anthracycline or during anthracycline
8. more than 250mg/m2 of anthracyclines
9. hypersensitivity of drug
10. interstitial pneumonitis or pulmonary fibrosis
11. positive HBs
12. antipsychotic medication
13. doctor's judgement

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
time to treatment failure

Secondary Outcome Measures

Name	Time	Method
progression-free survival
overall survival
response rate
adverse events

Trial Locations

Locations (1)

National Cancer Center Hospital; 🇯🇵 Chuo-ku, Tsukiji, 5-1-1, Tokyo, Japan