A Multicenter Randomized Phase III Study to Compare Capecitabine Alone or in Combination With Trastuzumab in Patients With HER2 Positive Metastatic Breast Cancer and Progression After Previous Treatment With Trastuzumab
Overview
- Phase
- Phase 3
- Intervention
- Capecitabine
- Conditions
- Breast Cancer
- Sponsor
- German Breast Group
- Enrollment
- 482
- Locations
- 1
- Primary Endpoint
- Any progression of disease or disease related death of a patient
- Status
- Completed
- Last Updated
- 15 years ago
Overview
Brief Summary
This study is done in patients having Breast Cancer with metastasis (patients with positive receptor HER2) whose disease progressed after receiving Trastuzumab.
The primary objective of this study is to compare the time until disease progression between the Treatment Arm CAPECITABINE and the Treatment Arm CAPECITABINE + TRASTUZUMAB
The study has also other secondary and tertiary objectives.
Detailed Description
Trial design: Prospective, multi-center, controlled, non blinded, randomized phase III Study Treatment: Patients with HER2 positive metastatic breast cancer and progression after previous treatment with trastuzumab are being randomized to either: A. Capecitabine 2500 mg/m² orally day 1-14 q day 22 until progression \* and discontinuation of Trastuzumab B. Capecitabine and Trastuzumab: Capecitabine 2500 mg/m² orally day 1-14 q day 22 until progression \* Trastuzumab 6 mg/kg body weight every 3 weeks i.v. as a 90 min infusion until progression \* Objectives: Primary objective: To compare the time to disease progression in patients with HER2 positive metastatic breast cancer and progression after previous treatment with trastuzumab randomized to capecitabine alone or in combination with trastuzumab. Secondary objectives: To compare the objective response rate between the two arms To compare the duration of response To compare the clinical benefit defined as CR, PR, or stable disease \> 24 weeks between the two arms To evaluate the safety of the capecitabine + trastuzumab combination To compare overall survival between the two arms Tertiary objective: To determine the HER2 status in tissue collected directly before study entry
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- •Pathologically confirmed carcinoma of the breast.
- •Locally advanced or metastatic stage of disease not suitable for surgery or radiotherapy alone.
- •HER2-overexpression of the primary or metastatic tumor tissue detected by immunohistochemistry (DAKO) 3+ or gene namplification detected by FISH. HER2-positive primary tumours with HER2-negative metastasis can be included.
- •Disease progression during or after previous chemotherapy and trastuzumab treatment as follows (Trastuzumab has to be given previously for at least 12 weeks, treatment free interval of trastuzumab for a maximum of 6 weeks):
- •Taxanes + trastuzumab given as adjuvant therapy
- •Taxanes + trastuzumab given as first line therapy for palliation
- •Trastuzumab given as first line therapy for palliation alone or in combination with chemotherapeutic agents other than capecitabine or taxanes
- •No more than 1 chemotherapy for palliation (max. Adriamycin dose \< or = 400 mg/m²; Epirubicin \< or = 600 mg/m²)
- •Patients must have either measurable or nonmeasurable target lesions according to the RECIST criteria (see Appendix 6)
Exclusion Criteria
- Not provided
Arms & Interventions
Capecitabine
Capecitabine 2500 mg/m² orally day 1-14 q day 22 until progression and discontinuation of Trastuzumab.
Intervention: Capecitabine
Capecitabine and Trastuzumab
Capecitabine 2500 mg/m² orally day 1-14 q day 22 until progression + Trastuzumab 6 mg/kg body weight every 3 weeks i.v. as a 90 min infusion until progression
Intervention: Capecitabine
Capecitabine and Trastuzumab
Capecitabine 2500 mg/m² orally day 1-14 q day 22 until progression + Trastuzumab 6 mg/kg body weight every 3 weeks i.v. as a 90 min infusion until progression
Intervention: Trastuzumab
Outcomes
Primary Outcomes
Any progression of disease or disease related death of a patient
Secondary Outcomes
- Any response documented according to the RECIST Criteria
- Time from CR or PR until progression of disease or death due to any cause
- Any response and stable disease of >24 weeks duration documented according to the RECIST Criteria
- Any grade III/IV toxicity (NCI-CTC version2.0).Premature treatment discontinuation
- Any death of a patient