Hormone Therapy and Chemotherapy in Treating Perimenopausal or Postmenopausal Women With Node-Positive Breast Cancer (12-93)
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| ClinicalTrials.gov Identifier: NCT00002529 |
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Recruitment Status :
Completed
First Posted : July 29, 2004
Last Update Posted : April 4, 2013
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer | Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: epirubicin hydrochloride Drug: tamoxifen citrate Drug: toremifene | Phase 3 |
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 (Clinical Trial) |
| Actual Enrollment : | 452 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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. |
| Study Start Date : | May 1993 |
| Actual Primary Completion Date : | August 2010 |
| Actual Study Completion Date : | August 2010 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: AC with concurrent tamoxifen
AC for 4 cycles with concurrent tamoxifen for 5 years
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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. |
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Experimental: AC followed by tamoxifen
AC for 4 cycles followed by tamoxifen to 5 years from randomization.
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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. |
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Experimental: Tamoxifen alone
Tamoxifen alone for 5 years.
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Drug: tamoxifen citrate
Tamoxifen 20 mg daily. |
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Experimental: AC with concurrent toremifene
AC for 4 cycles with concurrent toremifene for 5 years.
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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. |
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Experimental: AC followed by toremifene
AC for 4 cycles followed by toremifene to 5 years from randomization.
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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. |
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Experimental: Toremifene alone
Toremifene alone for 5 years.
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Drug: toremifene
Toremifene 60 mg daily. |
- Overall survival [ Time Frame: 17 years after randomization ]Time from randomization to death.
- 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.
- Quality of life [ Time Frame: 17 years from randomization ]Quality of life will be assessed using QL Questionnaires of IBCSG.
- Toxicity [ Time Frame: 17 years after randomization ]Assessment of toxicity according to standard criteria.
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| Ages Eligible for Study: | up to 70 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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)
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): NCT00002529
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| Study Chair: | Edda Simoncini, MD | Spedali Civili di Brescia |
| Responsible Party: | International Breast Cancer Study Group |
| ClinicalTrials.gov Identifier: | NCT00002529 |
| Other Study ID Numbers: |
CDR0000078385 IBCSG-12-93 ( Other Identifier: International Breast Cancer Study Group ) EU-93015 NCI-F93-0010 |
| First Posted: | July 29, 2004 Key Record Dates |
| Last Update Posted: | April 4, 2013 |
| Last Verified: | July 2012 |
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stage II breast cancer stage IIIA breast cancer |
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Tamoxifen Toremifene Cyclophosphamide Doxorubicin Liposomal doxorubicin Epirubicin Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Selective Estrogen Receptor Modulators Estrogen Receptor Modulators |