Hormone Therapy and Chemotherapy in Treating Perimenopausal or Postmenopausal Women With Node-Positive Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: epirubicin hydrochloride; Drug: tamoxifen citrate; Drug: toremifene

• Registration Number: NCT00002529
• Lead Sponsor: ETOP IBCSG Partners Foundation

Brief Summary

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the uptake of estrogen. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with hormone therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy during or after combination chemotherapy or hormone therapy alone in treating perimenopausal or postmenopausal women who have stage II or stage IIIA breast cancer.

Detailed Description

OBJECTIVES: I. Compare overall survival and local and systemic disease-free survival produced by adjuvant chemoendocrine therapy with 4 courses of anthracycline/cyclophosphamide and concurrent vs. sequential tamoxifen (TMX) or toremifene (TOR) in peri- and postmenopausal women with node-positive breast cancer who are considered suitable for endocrine therapy alone. II. Evaluate these same endpoints in patients randomized to chemoendocrine therapy vs. endocrine therapy alone. III. Evaluate these same endpoints in patients randomized to TMX vs. TOR as the endocrine therapy agent. IV. Compare the quality of life of patients treated on these regimens. V. Compare the toxic effects of these regimens.

OUTLINE: This is a randomized study. Patients are stratified by type of primary therapy and participating institution. Therapy must begin within 6 weeks of surgery. Patients in the first group receive doxorubicin (or epirubicin) and cyclophosphamide every 28 days for a total of 4 cycles and oral tamoxifen daily for 5 years, beginning day 1 of chemotherapy. Patients in the second group receive the same chemotherapy with oral tamoxifen initiated on day 8 of the fourth chemotherapy cycle and continued for 5 years. Patients in the third group receive oral tamoxifen daily for 5 years. Patients in the fourth group are treated the same as the first group, only tamoxifen is replaced by toremifene. Patients in the fifth group are treated the same as the second group, only tamoxifen is replaced by toremifene. Patients in the sixth group receive oral toremifene daily for 5 years. The timing of optional radiotherapy for patients with less than total mastectomy in each group is based on institutional policy; radiotherapy is administered for 5-6 weeks to the remaining breast tissue, chest wall, and lung. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and yearly thereafter.

PROJECTED ACCRUAL: 1,140 patients will be accrued over approximately 9 years, with 1 additional year of follow-up.

Study Timeline

• Study Start: 1993-05
• Study First Submitted: 1999-11-01
• Study First Submitted QC: 2004-07-28
• Study First Posted: 2004-07-29
• Primary Completion: 2010-08
• Study Completion: 2010-08
• Status Verified: 2012-07
• Last Update Submitted: 2013-04-03
• Last Update Posted: 2013-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 452

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AC with concurrent tamoxifen	cyclophosphamide	AC for 4 cycles with concurrent tamoxifen for 5 years
AC with concurrent tamoxifen	doxorubicin hydrochloride	AC for 4 cycles with concurrent tamoxifen for 5 years
AC with concurrent tamoxifen	epirubicin hydrochloride	AC for 4 cycles with concurrent tamoxifen for 5 years
AC with concurrent tamoxifen	tamoxifen citrate	AC for 4 cycles with concurrent tamoxifen for 5 years
AC followed by tamoxifen	epirubicin hydrochloride	AC for 4 cycles followed by tamoxifen to 5 years from randomization.
AC followed by tamoxifen	tamoxifen citrate	AC for 4 cycles followed by tamoxifen to 5 years from randomization.
Tamoxifen alone	tamoxifen citrate	Tamoxifen alone for 5 years.
AC with concurrent toremifene	cyclophosphamide	AC for 4 cycles with concurrent toremifene for 5 years.
AC with concurrent toremifene	doxorubicin hydrochloride	AC for 4 cycles with concurrent toremifene for 5 years.
AC followed by toremifene	cyclophosphamide	AC for 4 cycles followed by toremifene to 5 years from randomization.
AC with concurrent toremifene	epirubicin hydrochloride	AC for 4 cycles with concurrent toremifene for 5 years.
AC with concurrent toremifene	toremifene	AC for 4 cycles with concurrent toremifene for 5 years.
AC followed by toremifene	epirubicin hydrochloride	AC for 4 cycles followed by toremifene to 5 years from randomization.
AC followed by toremifene	toremifene	AC for 4 cycles followed by toremifene to 5 years from randomization.
Toremifene alone	toremifene	Toremifene alone for 5 years.
AC followed by tamoxifen	doxorubicin hydrochloride	AC for 4 cycles followed by tamoxifen to 5 years from randomization.
AC followed by tamoxifen	cyclophosphamide	AC for 4 cycles followed by tamoxifen to 5 years from randomization.
AC followed by toremifene	doxorubicin hydrochloride	AC for 4 cycles followed by toremifene to 5 years from randomization.

Primary Outcome Measures

Name	Time	Method
Overall survival	17 years after randomization	Time from randomization to death.

Secondary Outcome Measures

Name	Time	Method
Quality of life	17 years from randomization	Quality of life will be assessed using QL Questionnaires of IBCSG.
Toxicity	17 years after randomization	Assessment of toxicity according to standard criteria.
Disease-free and systemic disease-free survival.	17 years from randomization	Time from randomization to recurrence, metastasis, appearance of a second primary tumor or death.

Trial Locations

Locations (20)

Universitaetsspital; 🇨🇭 Zurich, Switzerland

Royal Prince Alfred Hospital, Sydney; 🇦🇺 Sydney, New South Wales, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Sir Charles Gairdner Hospital, Perth; 🇦🇺 Perth, Western Australia, Australia

Hopital des Cadolles, Neuchatel; 🇨🇭 Neuchatel, Switzerland

Universita di Brescia; 🇮🇹 Brescia, Italy

Ospedale Civile Rimini; 🇮🇹 Rimini, Italy

Ospedale San Eugenio; 🇮🇹 Rome, Italy

Anti-Cancer Council of Victoria, Melbourne; 🇦🇺 Carlton South, Victoria, Australia

Newcastle Mater Misericordiae Hospital; 🇦🇺 Newcastle, New South Wales, Australia

Centro di Riferimento Oncologico - Aviano; 🇮🇹 Aviano, Italy

Istituto Europeo Di Oncologia; 🇮🇹 Milano, Italy

Institute of Oncology, Ljubljana; 🇸🇮 Ljubljana, Slovenia

Auckland Adventist Hospital; 🇳🇿 Auckland, New Zealand

Inselspital, Bern; 🇨🇭 Bern, Switzerland

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Groote Schuur Hospital, Cape Town; 🇿🇦 Cape Town, South Africa

University Hospital; 🇨🇭 Basel, Switzerland

Sahlgrenska University Hospital; 🇸🇪 Gothenburg (Goteborg), Sweden

Kantonsspital - Saint Gallen; 🇨🇭 Saint Gallen, Switzerland