Clinical trial NCT00190489: A Trial of Doxorubicin/Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D for Metastatic Breast Cancer
Official title: Phase III Trial of Doxorubicin /Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D (AC-D) as Front-line Chemotherapy for Metastatic Breast Cancer: Japan Clinical Oncology Group Trial (JCOG9802)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Neoplasm Metastasis
Keywords: metastatic breast cancer
drug therapy
doxorubicin
docetaxel
Lead sponsor: Japan Clinical Oncology Group
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Labour and Welfare, Japan
First posted: 2005-09-19
Enrollment: 450
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: time to treatment failure
Secondary outcomes:
measure: overall survival
measure: progression-free survival
measure: response rate
measure: adverse events
Other outcomes:
Locations:
city: Chuo-ku, Tsukiji, 5-1-1
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
affiliation: National Shikoku Cancer Center
name: Shigemitsu Takashima, MD, PhD
role: STUDY_CHAIR
References: