Phase III Multicenter Randomized Open-label Study of Irinotecan Plus Capecitabine Versus Capecitabine in Patients Previously Treated With Anthracycline and Taxane for HER2 Negative Metastatic Breast Cancer[PROCEED]
20 Years
N/A
Female
Metastatic Breast Cancer
Trial Information
Phase III Multicenter Randomized Open-label Study of Irinotecan Plus Capecitabine Versus Capecitabine in Patients Previously Treated With Anthracycline and Taxane for HER2 Negative Metastatic Breast Cancer[PROCEED]
Prior to enrollment, patients will be confirmed for hormone and HER2 receptor status.
Patients may have either measurable and/or evaluable metastatic lesions which are able to be
assessed by chest, abdomen CT and bone scan performed within 28 days prior to start of
treatment.
- Capecitabine alone arm: 1250 mg/m2, BID, day 1-14, every 3 weeks
- Irinotecan plus capecitabine arm : Irinotecan 80 mg/m2, day 1 and 8, every 3 weeks +
capecitabine 1000 mg/m2, BID, day 1-14, every 3 weeks.
Randomization will be done using a random block size permutation method and stratified based
on : hormone receptor status (negative vs. positive), first line vs. more than second lines,
visceral metastasis (negative vs. positive).
Treatment will continue until disease progression, death, or discontinuation due to side
effects of drugs or refusal by patients.
The primary objective of this study is to estimate the PFS of capecitabine and irinotecan in
patients with anthracycline and taxane- pretreated metastatic breast cancer, which will be
estimated by the Kaplan-Meier method and compared by log-rank test. Overall survival will be
also estimated by same method. The secondary statistical analysis consisting of an
estimation of the complete and partial response rates and response rates of the treatment
will be calculated as the ratio of the number of complete and partial responders to the
total number of evaluable patients and toxicity profile, which will be estimated as the
ratio of the number of occurrence to the total number of evaluable patients. A 95%
confidence interval for the response rate is computed based on the binomial distribution
function. The analysis for reporting the final treatment results will be undertaken when
each patient has been potentially followed for a minimum of 12 months. The overall survival
and progression free survival, and their respective medians will be estimated with 95%
confidence intervals.
Inclusion Criteria:
- Histologically confirmed stage IV or recurrent breast cancer
- HER2 negative disease, or HER2 unknown disease not eligible for anti-HER2 therapy
- ECOG performance status 0-2
- Age ≥ 20 years
- Patients who received anthracycline based chemotherapy in the (neo)adjuvant or
metastatic setting and experienced disease progression on taxane based chemotherapy
in the metastatic setting, or patients who experienced disease recurrence within 1
year after completion of (neo)adjuvant anthracycline and taxane based chemotherapy
- In case of patients treated with capecitabine in an adjuvant setting, disease
recurrence should not be occurred within 1 year after completion of capecitabine
chemotherapy
- Patients with brain metastasis can be enrolled when they don't need any treatment
regarding to brain metastasis
- Previous any chemotherapy and radiotherapy should be completed at least 3 weeks
before randomization- Measurable or evaluable disease according to the Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [21]
- Adequate hematopoietic function: absolute granulocyte count ≥ 1,500/mm3, platelet ≥
100,000/mm3, hemoglobin ≥ 10g/mm3
- Adequate hepatic function: total bilirubin ≤ 1.5mg/dL, alkaline phosphatase(ALP) ≤
2.5 x UNL, AST/ALT ≤ 2x UNL, or if liver function abnormalities due to underlying
malignancy exists, AST/ALT ≤ 2.5 x UNL, total bilirubin ≤ 3.0mg/dL, (ALP) ≤ 5 x UNL
in cases with bone metastasis; ALP ≤ 5 x UNL
- Adequate renal function : serum creatinine ≤ 1.5mg/dL
- Ability to understand and comply with protocol during study period
- Patients should sign a written informed consent before study entry
Exclusion Criteria:
- Pregnant or lactating women
- Patients who receive irinotecan or capecitabine for metastatic breast cancer
treatment
- Patients with HER2 positive breast cancer
- Grade 2 or greater peripheral neuropathy
- Patients with symptomatic brain metastasis
- Prior unanticipated severe reaction to fluropyrimidine therapy or known sensitivity
to 5-fluorouracil
- Patients who have history of cancer other than in situ cervical cancer or
non-melanotic skin cancer
- Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedure
affecting absorption, uncontrolled GI disease (e.g. Crohn's disease, ulcerative
colitis)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression free survival (PFS)
Outcome Description:
Day between the date of enrollment to the date of disease progression or death
Outcome Time Frame:
The analysis for reporting the final treatment results will be undertaken when each patient has been potentially followed for a minimum of 12 months
Safety Issue:
No
Principal Investigator
Jungsil Ro
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cencer Center, Korea
Authority:
South Korea: Institutional Review Board
Study ID:
NCCCTS-11-536
NCT ID:
NCT01501669
Start Date:
June 2011
Completion Date:
February 2014
Related Keywords:
- Metastatic Breast Cancer
- irinotecan
- capecitabine
- metastatic breast cancer
- Breast Neoplasms
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