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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00004205
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : December 12, 2017
Sponsor:
Collaborators:
UNICANCER
Danish Breast Cancer Cooperative Group
Information provided by (Responsible Party):
ETOP IBCSG Partners Foundation

Tracking Information
First Submitted Date  ICMJE January 21, 2000
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date December 12, 2017
Study Start Date  ICMJE March 1998
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2015)		 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
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2015)
  • 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
  • Safety [ Time Frame: 5 years after randomization. ]
    Morbidity information will be recorded using the Adverse Event Form (AE).
  • 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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer
Official Title  ICMJE A Phase III Study to Evaluate Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors
Brief Summary

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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: letrozole
    Letrozole 2.5 mg daily oral administration.
  • Drug: tamoxifen citrate
    Tamoxifen 20 mg daily oral administration.
Study Arms  ICMJE
  • Experimental: Tamoxifen
    Tamoxifen for 5 years after randomization.
    Intervention: Drug: tamoxifen citrate
  • Experimental: Letrozole
    Letrozole for 5 years after randomization.
    Intervention: Drug: letrozole
  • Experimental: Tamoxifen, then letrozole
    Tamoxifen for 2 years after randomization, then letrozole for the next 3 years.
    Interventions:
    • Drug: letrozole
    • Drug: tamoxifen citrate
  • Experimental: Letrozole, then tamoxifen
    Letrozole for 2 years after randomization, then tamoxifen for the next 3 years.
    Interventions:
    • Drug: letrozole
    • Drug: tamoxifen citrate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2012)		 8028
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 30, 2016
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 30 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   France,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00004205
Other Study ID Numbers  ICMJE CDR0000067451
IBCSG-18-98
DAN-DBCG-IBCSG-1-98
FRE-FNCLCC-IBCSG-1-98
EU-99022
NOVARTIS-2026703019
BIG-1-98
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party ETOP IBCSG Partners Foundation
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE ETOP IBCSG Partners Foundation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • UNICANCER
  • Danish Breast Cancer Cooperative Group
Investigators  ICMJE
Study Chair: Beat Thurlimann, MD Cantonal Hospital of St. Gallen
Study Chair: Louis Mauriac, MD Institut Bergonié
Study Chair: Henning T. Mouridsen, MD, PhD Rigshospitalet, Denmark
PRS Account ETOP IBCSG Partners Foundation
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP