Overview

A Study to Compare ETC vs. EC-TX and Ibandronate vs. Observation in Patients With Node-positive Primary Breast Cancer (GAIN)

Status:
Completed
Trial end date:
2014-06-01
Target enrollment:
0
Participant gender:
Female
Summary
In the recent AGO-study, a dose-dense and dose-intensified sequence of Epirubicin - Paclitaxel - Cyclophosphamide has shown superior efficacy compared to a conventionally dosed sequence of Epirubicin / Cyclophosphamid and Paclitaxel and was therefore chosen as standard treatment in this study. The experimental arm of EC-TX combines several strategies: the combination of EC will be administered every 2 weeks as a dose-dense regimen, the combination of TX can also be considered as dose-dense due to the weekly application of paclitaxel. Furthermore there is clinical evidence, that a combination of capecitabine and Paclitaxel provide synergistic effects with improved tumour response. A randomized phase III study could demonstrate a survival benefit of a combination of capecitabine with Docetaxel in patients with metastatic breast cancer. This synergistic effect is probably based on the preclinical observed taxane-mediated up-regulation of thymidine phosphorylase in the tumour cell, which give drive to an increased transformation of capecitabine to its active form 5-Fluorouracil. Apart from this synergy, the EC-TX regimen includes now 4 highly active compounds for the treatment of breast cancer. The total doses of Epirubicin and Paclitaxel are identical in both arms. The dosage of Cyclophosphamide is lower in the experimental arm, which is preferred due to the induction of leukaemia at higher doses of Cyclophosphamide. The duration of both arms with 18 and 20 weeks is nearly similar. The 2 by 2 factorial design of the trial provides the additional possibility to explore the efficacy of a bisphosphonate as another strategy to further improve the prognosis of node positive breast cancer.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
German Breast Group
Treatments:
Capecitabine
Cyclophosphamide
Epirubicin
Ibandronic acid
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, Histologically confirmed
unilateral or bilateral primary carcinoma of the breast Age at diagnosis at least 18 years
and biologically younger than 65 years Adequate surgical treatment with histological
complete resection (R0) of the tumor and at least 10 axillary nodes At least one
histological involved axillary or internal mammarian lymph node No evidence for distant
metastasis after complete diagnostic work up Primary wound healing from breast surgery
without signs of infection Performance Status ECOG < 2 Estimated life expectancy of at
least 10 years irrespective of the diagnosis of breast cancer The patient must be
accessible for treatment and follow-up. Patients registered on this trial must be treated
and followed at the participating center which could be the Principal or an Co-
investigator's site

Exclusion Criteria:

Known hypersensitivity reaction to the compounds or incorporated substances or known
dihydropyrimidine dehydrogenase (DHP) deficiency.

Inadequate organ function including: ANC < 1.5 G/l, Platelets < 100 G/l , Transaminases,
Creatinine or Bilirubin > 1.25 times above upper normal limits (UNL), AP > 3 times above
UNL, Creatinine Clearance < 30ml/min (if Creatinine is above UNL, according to
Cockroft-Gault), severe and relevant co-morbidity that would interact with the application
of cytotoxic agents or the participation in the study Insufficient and uncompensated
cardiac function with LVEF below the normal range of the institution, history of severe
heart disease, myocardial infarction within the last 6 months, cardiac arrhythmias LOWN II
Evidence for infection including wound infections, HIV, Hepatitis Secondary malignancy,
except curatively treated basalioma of the skin and carcinoma in situ of the cervix Time
since axillary dissection > 3 months (optimal < 1 month) Non-operable breast cancer
Previous and already (neoadjuvant or adjuvant) treated invasive breast carcinoma Previous
or concurrent anti-tumor treatment for any reason Simultaneous therapy with Sorivudine or
Brivudine as virostatics, immunosuppressive treatment or concurrent treatment with
aminoglycosides Pregnancy or lactation period. Adequate non hormonal contraception is a
prerequisite in premenopausal patients Concurrent treatment with other experimental drugs.
Participation in another clinical trial with any investigational not marketed drug within
30 days prior to study entry.

Male patients