Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer (BIG 1-98)

December 8, 2017 updated by: ETOP IBCSG Partners Foundation

A Phase III Study to Evaluate Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells. If is not yet known which treatment regimen is most effective for breast cancer.

PURPOSE: Randomized double-blind phase III trial to compare the effectiveness of letrozole with that of tamoxifen in treating postmenopausal women who have breast cancer that has been surgically removed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare adjuvant letrozole vs tamoxifen administered for 5 years in postmenopausal women with operable, hormone receptor-positive breast cancer.
  • Compare these treatment regimens given sequentially vs continuously in this patient population.
  • Compare these treatment regimens in terms of overall survival, disease-free and systemic-free survival, safety, and tolerability in this patient population.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to adjuvant chemotherapy (prior therapy vs no prior or concurrent therapy vs concurrent therapy), prior surgery (modified radical mastectomy vs a lesser surgical procedure), and participating center. Patients are randomized to one of four treatment arms.

  • Arm I: Patients receive adjuvant oral tamoxifen daily for 5 years.
  • Arm II: Patients receive adjuvant oral letrozole daily for 5 years.
  • Arm III: Patients receive adjuvant oral tamoxifen daily for 2 years followed by adjuvant oral letrozole daily for 3 years.
  • Arm IV: Patients receive adjuvant oral letrozole daily for 2 years followed by adjuvant oral tamoxifen daily for 3 years.

Patients may receive concurrent radiotherapy. Some patients receive concurrent adjuvant chemotherapy beginning within 8 weeks after surgery and continuing for no more than 6 months.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 5,180 patients (1,295 per treatment arm) will be accrued for this study within 6 years.

Study Type

Interventional

Enrollment (Actual)

8028

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

  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
  • France
      • Bordeaux, France, 33076
        • Institut Bergonie
  • Switzerland
      • St. Gallen, Switzerland, CH-9007
        • Kantonsspital - St. Gallen

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

30 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed resectable adenocarcinoma of the breast

    • pT1, pT2, pT3, or minimal dermal involvement on pathology only

    • pN0, pN1, pN2, or M0

      • Negative nodal status

        • At least 8 nodes are negative

      • Unknown nodal status

        • Less than 8 nodes examined and no pathological finding

      • Positive nodal status

        • Any positive finding independent of the number of nodes examined
    • Negative sentinel node or no prior nodal dissection allowed if all other criteria met

  • Must have had total mastectomy, lumpectomy, or quadrantectomy

    • Should have prior chest wall radiotherapy after segmental mastectomy or histopathologic T4 dermal involvement
  • Stage I, II, or IIIa allowed if the tumor is completely removed macroscopically and margins of the resected tumor are microscopically free of tumor
  • Must undergo chest wall radiotherapy or second resection if microscopic disease at the mastectomy margins
  • No bilateral disease except in situ disease, either ductal or lobular of the contralateral breast

  • Postmenopausal

    • Regardless of prior hormonal replacement therapy (HRT) or hysterectomy:

      • Bilateral oophorectomy and any age
      • Radiologic castration and amenorrheic for at least 3 months and any age
      • Not postmenopausal at the start of adjuvant chemotherapy AND and completed at least 6 courses of prior cyclophosphamide, methotrexate, and fluorouracil (CMF) or at least 4 courses of prior anthracycline-cyclophosphamide continuation therapy and at least age 45 with follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) postmenopausal levels

    • No prior HRT:

      • Prior hysterectomy and less than age 55 with FSH/LH/E2 postmenopausal levels
      • Prior hysterectomy and at least age 55

    • No prior HRT or hysterectomy:

      • Amenorrhea more than 1 year and less than age 50
      • Amenorrhea more than 6 months and at least age 50

    • Prior HRT regardless of hysterectomy:

      • At least 1 month since prior HRT and less than age 55 with FSH/LH/E2 postmenopausal levels
      • At least 1 month since prior HRT and at least age 55
    • FSH/LH/E2 postmenopausal levels and uncategorized
  • No distant metastases, including bone scans showing hot spots unconfirmed as benign disease or skeletal pain of unknown cause
  • At least 10% hormone receptor-positive tumor cells

  • Hormone receptor status:

    • Estrogen receptor positive AND/OR
    • Progesterone receptor positive

PATIENT CHARACTERISTICS:

Age:

  • 30 and over

Sex:

  • Female

Menopausal status:

  • Postmenopausal

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • WBC greater than 3,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin greater than 10 g/dL

Hepatic:

  • Bilirubin less than 3.0 mg/dL
  • SGOT or SGPT less than 1.5 times upper limit of normal
  • No hepatic disease that would preclude study

Renal:

  • Creatinine less than 1.8 mg/dL
  • No renal disease that would preclude study

Cardiovascular:

  • No cardiovascular disease that would preclude study
  • Prior deep vein thrombosis allowed if medically stable

Pulmonary:

  • No lung embolism

Other:

  • No other prior or concurrent malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
  • No prior noncompliance to medical regimens
  • No other nonmalignant systemic diseases that would preclude follow-up
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior immunotherapy or biological response modifiers (e.g., interferon) allowed

Chemotherapy:

  • See Disease Characteristics
  • Prior adjuvant or neoadjuvant chemotherapy allowed
  • Concurrent adjuvant chemotherapy allowed

Endocrine therapy:

  • See Disease Characteristics
  • Prior neoadjuvant hormonal therapy allowed (e.g., antiestrogens, progestins, or aromatase inhibitors) if no more than 4 months duration and no disease progression
  • Prior corticosteroids allowed
  • At least 4 weeks since prior HRT
  • Prior adjuvant antiestrogen therapy allowed if less than 1 month duration and immediately after surgery, radiotherapy, and/or chemotherapy
  • Prior antiestrogens for chemoprevention allowed if at least 18 months between completion of chemoprevention and diagnosis
  • No other concurrent antiestrogens or aromatase inhibitors
  • No concurrent raloxifene
  • No concurrent systemic HRT with or without progestins of more than 3 months duration

Radiotherapy:

  • See Disease Characteristics
  • Concurrent radiotherapy allowed

Surgery:

  • See Disease Characteristics

Other:

  • At least 30 days since prior systemic investigational drugs
  • At least 7 days since prior topical investigational drugs
  • Concurrent bisphosphonates allowed

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tamoxifen
Tamoxifen for 5 years after randomization.
Drug: tamoxifen citrate
Tamoxifen 20 mg daily oral administration.
Experimental: Letrozole
Letrozole for 5 years after randomization.
Drug: letrozole
Letrozole 2.5 mg daily oral administration.
Experimental: Tamoxifen, then letrozole
Tamoxifen for 2 years after randomization, then letrozole for the next 3 years.
Drug: tamoxifen citrate
Tamoxifen 20 mg daily oral administration.
Drug: letrozole
Letrozole 2.5 mg daily oral administration.
Experimental: Letrozole, then tamoxifen
Letrozole for 2 years after randomization, then tamoxifen for the next 3 years.
Drug: tamoxifen citrate
Tamoxifen 20 mg daily oral administration.
Drug: letrozole
Letrozole 2.5 mg daily oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival.
Time Frame: Up to end of year 2015
Time from randomization to recurrence (including recurrence restricted to the breast after breast conserving treatment), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first, assessed up to end of year 2015, for a maximum of 17 years
Up to end of year 2015

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to end of year 2015
Time from randomization to death from any cause, assessed up to end of year 2015, for a maximum of 17 years
Up to end of year 2015
Safety
Time Frame: 5 years after randomization.
Morbidity information will be recorded using the Adverse Event Form (AE).
5 years after randomization.
Systemic relapse
Time Frame: Up to end of year 2015
Time from randomization to appearance of any recurrent or metastatic disease in sites other than the local mastectomy scar, the ipsilateral breast in case of breast conservation, or the contralateral breast, assessed up to end of year 2015, for a maximum of 17 years
Up to end of year 2015

Collaborators and Investigators

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

Sponsor

ETOP IBCSG Partners Foundation

Collaborators

UNICANCER
Danish Breast Cancer Cooperative Group

Investigators

  • Study Chair: Beat Thurlimann, MD, Cantonal Hospital of St. Gallen
  • Study Chair: Louis Mauriac, MD, Institut Bergonie
  • Study Chair: Henning T. Mouridsen, MD, PhD, Rigshospitalet, Denmark

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

March 1, 1998

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

June 30, 2016

Study Registration Dates

First Submitted

January 21, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

December 12, 2017

Last Update Submitted That Met QC Criteria

December 8, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067451
  • IBCSG-18-98
  • DAN-DBCG-IBCSG-1-98
  • FRE-FNCLCC-IBCSG-1-98
  • EU-99022
  • NOVARTIS-2026703019 (Other Identifier: Novartis)
  • BIG-1-98

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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 tamoxifen citrate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe