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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
International Breast Cancer Study Group
ClinicalTrials.gov Identifier:
NCT00002529
First received: November 1, 1999
Last updated: April 3, 2013
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: epirubicin hydrochloride
Drug: tamoxifen citrate
Drug: toremifene
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Therapy for Post/Perimenopausal Patients With Node Positive Breast Cancer Who Are Suitable for Endocrine Therapy Alone.

Resource links provided by NLM:


Further study details as provided by International Breast Cancer Study Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 17 years after randomization ] [ Designated as safety issue: No ]
    Time from randomization to death.


Secondary Outcome Measures:
  • Disease-free and systemic disease-free survival. [ Time Frame: 17 years from randomization ] [ Designated as safety issue: No ]
    Time from randomization to recurrence, metastasis, appearance of a second primary tumor or death.

  • Quality of life [ Time Frame: 17 years from randomization ] [ Designated as safety issue: No ]
    Quality of life will be assessed using QL Questionnaires of IBCSG.

  • Toxicity [ Time Frame: 17 years after randomization ] [ Designated as safety issue: Yes ]
    Assessment of toxicity according to standard criteria.


Enrollment: 452
Study Start Date: May 1993
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)

  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: NCT00002529

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

Additional Information:
Publications:

Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT00002529     History of Changes
Other Study ID Numbers: CDR0000078385, IBCSG-12-93, EU-93015, NCI-F93-0010
Study First Received: November 1, 1999
Last Updated: April 3, 2013
Health Authority: United States: Federal Government
Switzerland: Swissmedic

Keywords provided by International Breast Cancer Study Group:
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Doxorubicin
Epirubicin
Liposomal doxorubicin
Tamoxifen
Toremifene
Alkylating Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on October 28, 2014