Benefit of Adding Trastuzumab to Second Line Chemotherapy in Breast Cancer Patients Previously Treated With Trastuzumab
Eligible patients must receive vinorelbine plus capecitabine, with or without trastuzumab, until disease progression or unbearable toxicity. Cycles will be administered every 3 weeks. HER2 status must be locally assessed by immunohistochemistry (IHC). All 3+ patients are eligible. In 2+ patients, HER2 status must be confirmed by fluorescence in situ hybridization (FISH).
Principal outcome is clinical benefit (complete + partial responses + stable disease). Sample size in each arm has been estimated with the Fleming method. Previous data show a clinical benefit rate of vinorelbine plus capecitabine around 50%. The researchers assume trastuzumab can increase it by 20%. With an alpha error of 0.05 and 80% power, 37 patients per arm are needed.
This is a randomised phase II trial. With a minimum expected benefit rate of 50%, at least 36 patients are needed to choose, with a 90% of probability to be right, the best treatment arm, providing it increases benefit rate at least by 15%.
Assuming a drop-out rate of 10%, the total number of patients needed is 82, 41 per treatment arm.
Patients will be stratified as per investigational site, and presence of visceral metastatic lesion (liver, lung, pleura, heart, peritoneum, suprarenal glands). All patients must receive 2 cycles. If no disease progression is detected, treatment must continue until progression or unbearable toxicity.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Clinical Trial to Assess the Benefit of Adding Trastuzumab to Capecitabine and Vinorelbine as Second Line Treatment for HER2 Positive Breast Cancer Patients With Locally Advanced or Metastatic Disease, Progressing to a Previous Therapy Line With Trastuzumab and Taxanes|
- Clinical benefit rate (lasting for at least 24 weeks)
- Time to progression
- Overall response rate
- Response duration
- Safety profile
- Overall survival
- Quality of life
- Election of best treatment arm
|Study Start Date:||November 2005|
|Study Completion Date:||June 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
Active Comparator: Arm A
VX (vinorelbine and capecitabine)
Drug: Control Group
Vinorelbine 25 mg/m2 iv days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, p.o., b.i.d. days 1-14 each cycle (21 days).
Experimental: Arm B
Vinorelbine and capecitabine plus trastuzumab(VXH)
Trastuzumab, 4 mg/kg (charge dose in first week); Later 2 mg/kg iv. in following weeks plus Vinorelbine 25 mg/m2 iv days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, p.o., b.i.d. days 1-14 each cycle (21 days).
|Spanish Breast Cancer Research Group (GEICAM)|
|San Sebastián de los Reyes, Madrid, Spain, 28700|
|Study Chair:||Monserrat Muñoz, MD.,PhD.||Spanish Breast Cancer Research Group|