Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer (BIG 1-98)
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ClinicalTrials.gov Identifier: NCT00004205 |
Recruitment Status :
Completed
First Posted : January 27, 2003
Last Update Posted : December 12, 2017
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Breast Cancer | Drug: letrozole Drug: tamoxifen citrate | Phase 3 |
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 (Clinical Trial) |
Actual Enrollment : | 8028 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase III Study to Evaluate Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors |
Study Start Date : | March 1998 |
Actual Primary Completion Date : | December 2008 |
Actual Study Completion Date : | June 30, 2016 |
Arm | Intervention/treatment |
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Experimental: Tamoxifen
Tamoxifen for 5 years after randomization.
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Drug: tamoxifen citrate
Tamoxifen 20 mg daily oral administration. |
Experimental: Letrozole
Letrozole for 5 years after randomization.
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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.
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Drug: letrozole
Letrozole 2.5 mg daily oral administration. Drug: tamoxifen citrate Tamoxifen 20 mg daily oral administration. |
Experimental: Letrozole, then tamoxifen
Letrozole for 2 years after randomization, then tamoxifen for the next 3 years.
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Drug: letrozole
Letrozole 2.5 mg daily oral administration. Drug: tamoxifen citrate Tamoxifen 20 mg daily oral administration. |
- 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
- 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
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Ages Eligible for Study: | 30 Years to 120 Years (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed resectable adenocarcinoma of the breast
- pT1, pT2, pT3, or minimal dermal involvement on pathology only
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pN0, pN1, pN2, or M0
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Negative nodal status
- At least 8 nodes are negative
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Unknown nodal status
- Less than 8 nodes examined and no pathological finding
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Positive nodal status
- Any positive finding independent of the number of nodes examined
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- Negative sentinel node or no prior nodal dissection allowed if all other criteria met
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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
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Postmenopausal
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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
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No prior HRT:
- Prior hysterectomy and less than age 55 with FSH/LH/E2 postmenopausal levels
- Prior hysterectomy and at least age 55
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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
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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
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- 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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004205
Denmark | |
Rigshospitalet | |
Copenhagen, Denmark, 2100 | |
France | |
Institut Bergonie | |
Bordeaux, France, 33076 | |
Switzerland | |
Kantonsspital - St. Gallen | |
St. Gallen, Switzerland, CH-9007 |
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 |
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | ETOP IBCSG Partners Foundation |
ClinicalTrials.gov Identifier: | NCT00004205 |
Other Study ID Numbers: |
CDR0000067451 IBCSG-18-98 DAN-DBCG-IBCSG-1-98 FRE-FNCLCC-IBCSG-1-98 EU-99022 NOVARTIS-2026703019 BIG-1-98 |
First Posted: | January 27, 2003 Key Record Dates |
Last Update Posted: | December 12, 2017 |
Last Verified: | December 2017 |
stage I breast cancer stage II breast cancer stage IIIA breast cancer breast cancer in situ |
recurrent breast cancer ductal breast carcinoma lobular breast carcinoma in situ |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Tamoxifen Letrozole Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Aromatase Inhibitors |
Steroid Synthesis Inhibitors Enzyme Inhibitors Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Bone Density Conservation Agents |