Hormone Therapy and Chemotherapy in Treating Perimenopausal or Postmenopausal Women With Node-Positive Breast Cancer (12-93)

April 3, 2013 updated by: ETOP IBCSG Partners Foundation

Adjuvant Therapy for Post/Perimenopausal Patients With Node Positive Breast Cancer Who Are Suitable for Endocrine Therapy Alone.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

452

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Newcastle, New South Wales, Australia, NSW 2310
        • Newcastle Mater Misericordiae Hospital
      • Sydney, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital, Sydney
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
    • Victoria
      • Carlton South, Victoria, Australia, 3053
        • Anti-Cancer Council of Victoria, Melbourne
    • Western Australia
      • Perth, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital, Perth
  • Italy
      • Aviano, Italy, 33081
        • Centro di Riferimento Oncologico - Aviano
      • Brescia, Italy, 25124
        • Universita di Brescia
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia
      • Rimini, Italy, 47037
        • Ospedale Civile Rimini
      • Rome, Italy, 00144
        • Ospedale San Eugenio
  • New Zealand
      • Auckland, New Zealand, 5
        • Auckland Adventist Hospital
  • Slovenia
      • Ljubljana, Slovenia, Sl-1000
        • Institute of Oncology, Ljubljana
  • South Africa
      • Cape Town, South Africa, 7925
        • Groote Schuur Hospital, Cape Town
  • Sweden
      • Gothenburg (Goteborg), Sweden, S-413 45
        • Sahlgrenska University Hospital
  • Switzerland
      • Basel, Switzerland, CH-4031
        • University Hospital
      • Bern, Switzerland, CH-3010
        • Inselspital, Bern
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Neuchatel, Switzerland, 2000
        • Hopital des Cadolles, Neuchatel
      • Saint Gallen, Switzerland, CH-9007
        • Kantonsspital - Saint Gallen
      • Zurich, Switzerland, CH-8091
        • UniversitaetsSpital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS: Histologically proven stage T1-3, pN1, M0 carcinoma of the breast considered suitable for adjuvant treatment with endocrine therapy alone Estrogen receptor at least 10 fmol/mg cytosol protein or positive on immunohistochemical assay Potentially curative resection within 6 weeks of entry by one of the following: Total mastectomy with negative margins Breast-conserving procedure (lumpectomy or quadrantectomy) for tumors less than 5 cm Adequate re-resection or mastectomy within 4 weeks of initial surgery required if margins are positive after initial surgery Axillary clearance (not sampling) required at surgery, with at least 1 node positive upon histopathologic examination of at least 8 nodes Suspicious manifestations of metastatic disease (e.g., hot spots on bone scan, skeletal pain of unknown cause) must be proven benign No bilateral breast cancer Any mass in contralateral breast must be proven benign by biopsy

PATIENT CHARACTERISTICS: Age: 70 and under Sex: Women only Menopausal status: Peri/postmenopausal, i.e.: More than 6 months since last normal menstrual period (LNMP) with no prior hysterectomy and no hormone replacement therapy (HRT) Prior hysterectomy and no HRT and either age greater than 55 or age 55 or less with postmenopausal LH, FSH, and E2 levels On HRT and either age 50 or greater or LNMP more than 6 months prior to starting HRT Performance status: Not specified Hematopoietic: WBC greater than 4,000 Platelets greater than 100,000 Hepatic: Bilirubin less than 1.1 mg/dL (20 micromoles/L) AST less than 60 IU/L Renal: Creatinine less than 1.3 mg/dL (120 micromoles/L) Other: No nonmalignant systemic disease that would preclude protocol therapy or prolonged follow-up No psychiatric or addictive disorder that would preclude informed consent No prior or concurrent second malignancy except: Nonmelanomatous skin cancer Adequately treated in situ carcinoma of the cervix Geographically accessible for follow-up

PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer other than potentially curative surgery (see Disease Characteristics)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AC with concurrent tamoxifen
AC for 4 cycles with concurrent tamoxifen for 5 years
Drug: cyclophosphamide
cyclophosphamide 600 mg/m2 i.v. day 1) every 21 days
Drug: doxorubicin hydrochloride
doxorubicin 60 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: epirubicin hydrochloride
epirubicin 90 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: tamoxifen citrate
Tamoxifen 20 mg daily.
Experimental: AC followed by tamoxifen
AC for 4 cycles followed by tamoxifen to 5 years from randomization.
Drug: cyclophosphamide
cyclophosphamide 600 mg/m2 i.v. day 1) every 21 days
Drug: doxorubicin hydrochloride
doxorubicin 60 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: epirubicin hydrochloride
epirubicin 90 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: tamoxifen citrate
Tamoxifen 20 mg daily.
Experimental: Tamoxifen alone
Tamoxifen alone for 5 years.
Drug: tamoxifen citrate
Tamoxifen 20 mg daily.
Experimental: AC with concurrent toremifene
AC for 4 cycles with concurrent toremifene for 5 years.
Drug: cyclophosphamide
cyclophosphamide 600 mg/m2 i.v. day 1) every 21 days
Drug: doxorubicin hydrochloride
doxorubicin 60 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: epirubicin hydrochloride
epirubicin 90 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: toremifene
Toremifene 60 mg daily.
Experimental: AC followed by toremifene
AC for 4 cycles followed by toremifene to 5 years from randomization.
Drug: cyclophosphamide
cyclophosphamide 600 mg/m2 i.v. day 1) every 21 days
Drug: doxorubicin hydrochloride
doxorubicin 60 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: epirubicin hydrochloride
epirubicin 90 mg/m2 i.v. day 1) every 21 days, intravenous.
Drug: toremifene
Toremifene 60 mg daily.
Experimental: Toremifene alone
Toremifene alone for 5 years.
Drug: toremifene
Toremifene 60 mg daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 17 years after randomization
Time from randomization to death.
17 years after randomization

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ETOP IBCSG Partners Foundation

Investigators

  • Study Chair: Edda Simoncini, MD, Spedali Civili di Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 1993

Primary Completion (Actual)

August 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 28, 2004

First Posted (Estimate)

July 29, 2004

Study Record Updates

Last Update Posted (Estimate)

April 4, 2013

Last Update Submitted That Met QC Criteria

April 3, 2013

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000078385
  • IBCSG-12-93 (Other Identifier: International Breast Cancer Study Group)
  • EU-93015
  • NCI-F93-0010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on cyclophosphamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe