Studying the Benefits of Adjuvant Sequential vs. Combined Taxane Based Chemotherapy, Followed by Different Biological Treatment Strategies in Early, HER2-positive Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Philip Hepp, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT00670878
First received: April 30, 2008
Last updated: March 31, 2012
Last verified: March 2012
  Purpose

This is an open-label, multicenter randomized controlled, Phase III study comparing the disease free survival after randomisation in patients treated with 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide (FEC)-chemotherapy, followed by 3 cycles of Docetaxel (D)-chemotherapy versus 3 cycles of Epirubicin-Fluorouracil- Cyclophosphamide (FEC), followed by 3 cycles of Gemcitabine-Docetaxel(DG)- chemotherapy. Patients will be required to have HER2-neu positive disease and histopathological proof of axillary lymph node metastases (pN1-3) or high risk node negative, defined as: pT>=2 or histopathological grade 3, or age <= 35 or negative hormone receptor', but are not allowed to have evidence of distant disease. Patients will have to be entered into the study no later than 6 weeks after complete resection of the primary tumor. No other antineoplastic treatment other than surgical treatment, the defined cytotoxic and endocrine treatment and radiotherapy will be allowed prior to study entry and during the course of the study.


Condition Intervention Phase
Breast Cancer
Drug: 3 x FEC 3 x DOC / Gemcitabine
Drug: 3 x FEC 3 x DOC
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospectively Randomized Phase III Trial, Studying the Benefits of Adjuvant Sequential vs. Combined Taxane Based Chemotherapy, Followed by Different Biological Treatment Strategies in Early, HER2-positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: 5 y ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival time after randomization [ Time Frame: 5 Y ] [ Designated as safety issue: No ]
  • Distant disease free survival [ Time Frame: 5 Y ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 5 Y ] [ Designated as safety issue: No ]
  • Changes in quality of life over time as defined by EORTC QLQ-C30 and QLQBR23 questionnaire [ Time Frame: 5 Y ] [ Designated as safety issue: No ]
  • Skeletal related events [ Time Frame: 5 Y ] [ Designated as safety issue: No ]
  • Incidence of secondary primaries [ Time Frame: 5 Y ] [ Designated as safety issue: No ]
  • Endpoints of adjunct translational research program [ Time Frame: 5 Y ] [ Designated as safety issue: No ]

Estimated Enrollment: 799
Study Start Date: June 2008
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: 3 x FEC 3 x DOC / Gemcitabine
3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicin 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 75 mg/m² body surface area i.v. (D), and Gemcitabine 1000 mg/m² i.v. (30 min infusion) (G), administered on day 1, followed by Gemcitabine 1000 mg/m² i.v. (30 min infusion) on day 8, repeated on day 22
Active Comparator: B Drug: 3 x FEC 3 x DOC
3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicin 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 100 mg/m² body surface area i.v. (D), administered on day 1, repeated on day 22

  Eligibility

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

Inclusion Criteria:

  • Primary epithelial invasive carcinoma of the breast pT1-4, pN0-3, M0
  • Evidence of HER2-neu overexpressing (IHC +++) or amplifying (FISH +) tumor
  • Histopathological proof of axillary lymph node metastases (pN1-3) or high risk node negative, defined as at least two criteria of the following: 'pT³2, histopathological grade 3, age £ 35, negative hormone receptor'
  • Complete resection of the primary tumor with margins of resection free of invasive carcinoma not more than 6 weeks ago
  • Females >= 18 years of age
  • Performance Status <2 on ECOG-Scale
  • Adequate bone marrow reserve: leucocytes ³ 3.0 x 109/l and platelets ³ 100 x 109/l
  • Bilirubin within one fold of the reference laboratory's normal range, ASAT (SGOT), ALAT (SGPT) and AP within 1,5 fold of the reference laboratory's normal range for patients
  • Intention of regular follow up visits for the duration of the study
  • Ability to understand the nature of the study and to give written informed consent
  • Women of childbearing potential must agree to use an effective method of contraception (Pearl-Index < 1, e.g. , intrauterine devices or sterilization) during treatment and for at least 6 months thereafter.

Exclusion Criteria:

  • Inflammatory breast cancer
  • Previous or concomitant cytotoxic or other systemic antineoplastic treatment which is not part of this study
  • A second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin)
  • Cardiomyopathy with impaired ventricular function (NYHA > II), cardiac arrhythmias influencing LVEF and requiring medication, history of myocardial infarction or angina pectoris within the last 6 months, or arterial hypertension not being controlled by medication
  • Any known hypersensitivity reaction against docetaxel, epirubicin, cyclophosphamide, gemcitabine or any other medication included in the study protocol. The contraindication, warning notices and measures of precaution of the products, as notified in the product information, have to be respected
  • Instable diabetes mellitus, out of sufficient medical control
  • Use of any investigational agent within 3 weeks prior to inclusion
  • Patients in pregnancy or breast feeding (in premenopausal women contraception has to be assured)
  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: NCT00670878

Locations
Germany
Frauenklinik der Universität München Campus Innenstadt
Munich, Germany, 80337
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
  More Information

Additional Information:
No publications provided

Responsible Party: Philip Hepp, study doctor, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT00670878     History of Changes
Other Study ID Numbers: SUCCESS-B
Study First Received: April 30, 2008
Last Updated: March 31, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014