Three arm randomized parallel phase II/III study evaluating the efficacy and safety of the combinations Epirubicin and Taxotere® (ET), Taxotere® and Navelbine® (TN) and Navelbine® and Epirubicin (EN) as first line therapy in patients with metastatic breast cancer

ISRCTN ISRCTN33132357
DOI https://doi.org/10.1186/ISRCTN33132357
Protocol serial number NTR472
Sponsor VU University Medical Center (Netherlands)
Funders Amgen (Netherlands), Pfizer (Netherlands), Pierre Fabre (France), Sanofi-Aventis (France), VU University Medical Center (Netherlands)
Submission date
27/01/2006
Registration date
27/01/2006
Last edited
03/07/2009
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof E. Boven
Scientific

VU University Medical Center
Department of Medical Oncology
6 Z 170
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Study information

Primary study designInterventional
Study designmulticentre, randomised, active controlled, parallel group study
Secondary study designRandomised controlled trial
Scientific title
Study acronymETN study
Study objectivesPrimary objectives: To assess the efficacy in terms of response rate of the combinations Epirubicin and Taxotere (ET), Taxotere and Navelbine (TN) and Navelbine and Epiribicin (EN).
Secondary objectives: To determine progression free survival and toxicity profiles.
Ethics approval(s)Received from the local media ethics committee
Health condition(s) or problem(s) studiedBreast cancer
InterventionArm A: Epirubicin 75 mg/m2, day 1 and docetaxel 60 mg/m2 day 1
Arm B: Vinorelbine 20 mg/m2 day 1 + 8 and docetaxel 60 mg/m2 day 8 (closed January 2003)
Arm C: Epirubicin 75 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8.
One course consists of 21 days. Cycle is repeated every 3 weeks, for a maximum of 6 cycles.
Intervention typeDrug
PhasePhase II/III
Drug / device / biological / vaccine name(s)epirubicin, docetaxel (Taxotere®), vinorelbine (Navelbine®)
Primary outcome measure(s)

1. Time to progression
2. Response rate

Key secondary outcome measure(s)

1. Toxicity profile
2. Feasibility

Completion date01/12/2005

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target sample size at registration111
Key inclusion criteria1. Histologically proven breast cancer at first diagnosis. At study entry histological or cytological proof of metastasis is required in case of a single metastatic target lesion.
2. Female metastatic breast cancer patients
3. Measurable disease or evaluable disease (bone metastases only allowed)
4. Previous chemotherapy: Adjuvant: Patients may have had adjuvant and/or neoadjuvant chemotherapy but no more than 240 mg/m2 cumulative dose of prior doxorubicin or no more than 450 mg/m2 of epirubicin. Taxanes in adjuvant setting are allowed. However, there must be at least 12 months interval between the end of (neo-)adjuvant chemotherapy and protocol entry. This interval is not required for patients who received non-anthracycline/non-taxane adjuvant and/or neoadjuvant chemotherapy. No previous chemotherapy for metastatic breast cancer is allowed.
5. Previous hormonal treatment: Previous hormonal treatment is allowed provided discontinuation >4 weeks before start of study treatment
6. Previous radiation: Previous radiation therapy may have been given provided it is not the only site to assess response
7. Age >18 and <70 years
8. WHO performance status 0, 1 or 2
9. Laboratory requirements:
a. Hematology: White blood cell count >3.0 x 10^9/l (if WBC <3.0 x 10^9/l, Neutrophils should be >1.5 x 10^9/l), Platelets >100 x 10^9/l, Hemoglobin >10 g/dl (>6.2 mmol/l)
b. Hepatic function: Total bilirubin <1.00 times the upper-normal limits (UNL) of the institutional normal values. ASAT (SGOT) and/or ALAT (SGPT) <2.5 UNL, alkaline phosphatase <5 UNL (unless bone metastasis are present in the absence of any liver disorders). NB: Patients with ASAT and/or ALAT >1.5 UNL associated with alkaline phosphatase >2.5 UNL are not eligible for study.
c. Renal function: Serum creatinine <80 umol/l. If serum creatinine >80 umol/l, calculated creatinine clearance (Cockroft Gould) should be >60 ml/min
10. Normal left ventricular ejection fraction (LVEF) or superior to the lower limits of the institution (determined by either MUGA scan or ultrasound methods)
11. Patients must be accessible for treatment and follow-up
12. Measurability of the disease and evaluation of response according to RECIST criteria
13. Complete initial work-up within 3 weeks prior to first infusion
14. Written informed consent
Key exclusion criteria1. Prior chemotherapy for metastatic disease
2. Locally advanced inoperable breast cancer (Stage III B) as only manifestation of the disease
3. Non-measurable disease
4. Pregnant or lactating women or women of childbearing potential not using adequate contraception
5. History of prior malignancies (other than non melanoma skin cancer or excised cervical carcinoma in situ)
6. Clinical evidence of cerebral metastasis
7. Symptomatic peripheral neuropathy > grade 2 according to the NCI Common Toxicity Criteria
8. WHO PS >2
9. Concurrent treatment with other experimental drugs
10. Participation in another clinical trial with any investigational drug within 30 days prior to study screening
11. Concurrent treatment with any other anti-cancer therapy except for concomitant treatment with bisphosphonates, provided that bone metastases are not the only evaluable lesions for response to therapy (see measurability of disease and evaluation of response)
Date of first enrolment01/04/2001
Date of final enrolment01/12/2005

Locations

Countries of recruitment

  • Netherlands

Study participating centre

VU University Medical Center
Amsterdam
1007 MB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing plan
BMC - Part of Springer Nature Springer Nature