TBP Study With Capecitabine Plus Minus Trastuzumab

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
German Breast Group
ClinicalTrials.gov Identifier:
NCT00148876
First received: September 7, 2005
Last updated: February 22, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Capecitabine
Drug: Trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by German Breast Group:

Primary Outcome Measures:
  • Any progression of disease or disease related death of a patient

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 482
Study Start Date: September 2003
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Capecitabine
Capecitabine 2500 mg/m² orally day 1-14 q day 22 until progression and discontinuation of Trastuzumab.
Drug: Capecitabine
Capecitabine 2500 mg/m² orally day 1-14 q day 22
Experimental: 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
Drug: Capecitabine
Capecitabine 2500 mg/m² orally day 1-14 q day 22
Drug: Trastuzumab
Trastuzumab 6 mg/kg body weight every 3 weeks i.v.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 gene namplification 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 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
  6. No more than 1 chemotherapy for palliation (max. Adriamycin dose < or = 400 mg/m²; Epirubicin < or = 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 > or = 60%
  12. Age >18 years.
  13. Absolute neutrophil count > or =1,500 cells/microL, platelet count > or =100,000 cells/microL.
  14. Bilirubin < or = 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 < or = 2.0 mg/dl.
  16. Left ventricular ejection fraction (LVEF) by cardiac ultrasound of > or = 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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00148876

Locations
Germany
Johann Wolfgang Goethe Universität, Universitätsfrauenklinik
Frankfurt / Main, Hessen, Germany, 60590
Sponsors and Collaborators
German Breast Group
Hoffmann-La Roche
Investigators
Principal Investigator: Gunter von Minckwitz, Prof. Dr. German Breast Group Forschungs GmbH
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00148876     History of Changes
Other Study ID Numbers: GBG 26, BIG3-05
Study First Received: September 7, 2005
Last Updated: February 22, 2011
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by German Breast Group:
Progression after treatment with Trastuzumab
Metastatic Breast Cancer
Palliative Study

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Capecitabine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014