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 (Treatment Beyond Progression, TBP). - GBG26/TBP

• Conditions: Patients with HER2 positive metastatic breast cancer and progression after previous treatment with trastuzumab.

• Registration Number: EUCTR2005-002084-85-SI
• Lead Sponsor: GBG Forchungs GmBH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-11-24
• Last Update Posted: 15 July 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 482

Inclusion Criteria

1. 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.
2. Pathologically confirmed carcinoma of the breast.
3. Locally advanced or metastatic stage of disease not suitable for surgery or radiotherapy alone.
4. HER2-overexpression of the primary or metastatic tumor tissue detected by immunohistochemistry (DAKO) 3+ or genamplification detected by FISH. HER2-positive primary tumours with HER2-negative metastasis can be included.
5. 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 intervall of trastuzumab for a maximum of 6 weeks for treatment of advanced disease, 12 months for adjuvant trastuzumab):
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.
6. No more than 1 chemotherapy for palliation (max. Adriamycin dose less than or equal to 400 mg/m²; Epirubicin less than or equal to 600 mg/m²).
7. Patients must have either measurable or nonmeasurable target lesions according to the RECIST criteria (see Appendix 6).
8. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease.
9. At least 4 weeks since major surgery with full recovery.
10. Complete radiology and tumor measurement work up within 4 weeks prior to registration:
11. Karnofsky performance status evaluation greater than or equal to 60%.
12. Age >18 years.
13. Absolute neutrophil count greater than or equal to 1,500 cells/microliter, platelet count greater than or equal to 100,000 cells/microliter.
14. Bilirubin less than or equal to 2x the upper limit of normal for the institution (ULN); elevation of transaminases and alkaline phosphatase < 2.5x ULN or <5x ULN for patients with liver metastases.
15. Creatinine less than or equal to 2.0 mg/dl (corresponds to 177 µmol/L).
16. Left ventricular ejection fraction (LVEF) by cardiac ultrasound or MUGA scan of greater than or equal to 50%.
17. If of childbearing potential, pregnancy test is negative. In addition the patient agrees to use an effective method to avoid pregnancy for the duration of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.
2. Concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive and/or replacement therapy). Bisphosphonates may be continued.
3. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy with complete resolution of symptoms and of all steroids.
4. Life expectancy of less than 3 months.
5. Serious intercurrent medical or psychiatric illness that may interfere with the planned treatment (including severe pulmonary conditions, AIDS and serious active infection).
6. History of congestive heart failure or other significant uncontrolled cardiac disease.
7. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
8. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
9. Treatment with sorivudine or derivates e.g. brivudin.
10. Pregnant or nursing women.
11. Male patients.
12. The patient must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or Co- investigator’s site.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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 Objective: To compare the objective response rate between the two arms.<br>To compare the duration of response.<br>To compare the clinical benefit defined as CR, PR, or stable disease > 24 weeks between the two arms.<br>To evaluate the safety of the capecitabine + trastuzumab combination.<br>To compare overall survival between the two arms.<br>;Primary end point(s): Any progression of disease or disease related death of a patient.