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SWOG-8814 Tamoxifen With or Without Combination Chemotherapy in Postmenopausal Women Who Have Undergone Surgery for Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
North Central Cancer Treatment Group
Cancer and Leukemia Group B
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00929591
First received: June 26, 2009
Last updated: January 23, 2013
Last verified: January 2013

June 26, 2009
January 23, 2013
May 1989
August 2005   (final data collection date for primary outcome measure)
  • Disease-free survival [ Time Frame: eight years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: eight years ] [ Designated as safety issue: No ]
  • Toxicity/morbidity of treatment [ Time Frame: during treatment ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity/morbidity of treatment [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00929591 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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SWOG-8814 Tamoxifen With or Without Combination Chemotherapy in Postmenopausal Women Who Have Undergone Surgery for Breast Cancer
Phase III Comparison of Adjuvant Chemoendocrine Therapy With CAF and Concurrent or Delayed Tamoxifen to Tamoxifen Alone in Postmenopausal Patients With Involved Axillary Lymph Nodes and Positive Receptors

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving tamoxifen alone is more effective in treating breast cancer than giving tamoxifen together with chemotherapy or after chemotherapy.

PURPOSE: This randomized phase III trial is studying giving tamoxifen with or without combination chemotherapy to compare how well they work in treating postmenopausal women who have undergone surgery for breast cancer.

OBJECTIVES: I. Compare disease-free survival and overall survival of postmenopausal women with node-positive, estrogen and/or progesterone receptor-positive adenocarcinoma of the breast randomly assigned to postoperative adjuvant treatment with long-term (5 years) tamoxifen vs. CAF (cyclophosphamide/doxorubicin/fluorouracil) plus concurrent and long-term tamoxifen vs. CAF followed by long-term tamoxifen. II. Compare the relative toxicities of these three regimens.

OUTLINE: Randomized study. All patients are randomized on Arms I, II, and III. Lumpectomy patients must receive radiotherapy on Regimen A. At the discretion of the physician, mastectomy patients may receive radiotherapy on Regimen B for a tumor greater than 5 cm in diameter, 4 or more positive nodes, or extranodal extension of the tumor into the axillary fat. Patients randomized to Arm I who are to receive radiotherapy should begin as soon as feasible postoperatively; these patients may be irradiated while receiving tamoxifen. Patients on Arms II and III who are to receive radiotherapy are treated either postoperatively prior to registration or after completion of and recovery from 6 courses of CAF. Arm I: Antiestrogen Therapy. Tamoxifen, TMX, NSC-180973. Arm II: 3-Drug Combination Chemotherapy followed by Antiestrogen Therapy. CAF: Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; Fluorouracil, 5-FU, NSC-19893; followed by TMX. Arm III: 3-Drug Combination Chemotherapy plus Concurrent Antiestrogen Therapy. CAF; plus concurrent TMX. Regimen A: Radiotherapy. Irradiation of the breast and underlying chest wall and (optionally) of the supraclavicular area and, if indicated, the axilla, using megavoltage equipment with photon energies of up to 6 MV followed, if indicated, by a tumor bed boost using either electrons or iridium-192 (192-Ir) implants. Regimen B: Radiotherapy. Irradiation of the chest wall using either megavoltage photons via a tangential field or electrons via a direct field plus (optional) photon irradiation of the supraclavicular area and, if indicated, the axilla.

PROJECTED ACCRUAL: 350 patients will be randomized to Arm I and 530 patients each will be randomized to Arms II and III. Accrual should be completed in about 4 years, and 4 additional years will be required for follow-up.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: endocrine therapy
  • Drug: endocrine-modulating drug therapy
  • Drug: fluorouracil
  • Drug: tamoxifen citrate
  • Radiation: brachytherapy
  • Radiation: low-LET electron therapy
  • Radiation: low-LET photon therapy
  • Radiation: radiation therapy
  • Active Comparator: tamoxifen for five years
    tamoxifen for five years
    Interventions:
    • Drug: endocrine therapy
    • Drug: tamoxifen citrate
    • Radiation: brachytherapy
    • Radiation: low-LET electron therapy
    • Radiation: low-LET photon therapy
    • Radiation: radiation therapy
  • Experimental: CAF followed by tamoxifen for five years
    intermittent CAF X 6 courses followed by tamoxifen for five years
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: endocrine therapy
    • Drug: endocrine-modulating drug therapy
    • Drug: fluorouracil
    • Drug: tamoxifen citrate
    • Radiation: brachytherapy
    • Radiation: low-LET electron therapy
    • Radiation: low-LET photon therapy
    • Radiation: radiation therapy
  • Experimental: CAF with concurrent tamoxifen for five years
    intermittent CAF X 6 courses with concurrent tamoxifen for five years
    Interventions:
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: endocrine therapy
    • Drug: endocrine-modulating drug therapy
    • Drug: fluorouracil
    • Drug: tamoxifen citrate
    • Radiation: brachytherapy
    • Radiation: low-LET electron therapy
    • Radiation: low-LET photon therapy
    • Radiation: radiation therapy

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1558
March 2010
August 2005   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the breast No apocrine, adenoidcystic, or squamous carcinomas or sarcomas Pathologic Stage T1-3a, pathologic N1-2 (clinical N0-1), M0: Rendered free of gross tumor at surgery Primary tumor movable with respect to chest wall Axillary nodes movable with respect to chest wall and each other No preoperative edema of the arm, peau d'orange, skin ulceration, or inflammatory lesions One or more positive lymph nodes required No positive deep mastectomy margins or clinical skin involvement (focal microscopic dermal invasion or focal microscopic dermal lymphatic involvement allowed) No evidence of metastatic disease on pretherapy studies (including chest x-ray, bone scan, and mammogram) No bilateral invasive tumors Patients who had noninvasive ductal carcinoma in situ of the opposite breast and underwent prophylactic contralateral mastectomy are eligible Hormone receptor status: Positive for estrogen and/or progesterone receptors (at least 10 fmol/mg protein or unequivocally positive immunocytochemical assay for one or both) Participation in SWOG-8854 (flow cytometry) recommended

PATIENT CHARACTERISTICS: Age: Any age Sex: Females only Menopausal status: Postmenopausal as defined by 1 or more of the following: Bilateral oophorectomy at least 2 months prior to diagnosis of breast cancer (with or without estrogen therapy following surgery) Prior hysterectomy with at least 1 ovary remaining and either over 60 years old or with a postmenopausal FSH level Natural menopause (last menstrual period at least 1 year prior to registration or 4-12 months prior to registration with a postmenopausal FSH level) Treated with postmenopausal estrogen therapy and either over 55 years old or with a postmenopausal FSH level Performance status: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no more than 1.2 x normal Alkaline phosphatase no more than 1.2 x normal SGOT or SGPT no more than 1.2 x normal Renal: Creatinine no more than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension No history of ischemic heart disease or CHF Normal ejection fraction by MUGA (required only if deemed clinically necessary for assessment) Other: No medical condition that would preclude protocol therapy: No severe diabetes No active ulcer disease No significant psychiatric disease No second malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer Curatively treated Stage I cervical carcinoma Pretreatment mammogram and chest x-ray completed no more than 3 months preoperatively; blood/body fluid analyses to determine eligibility completed within 14 days prior to registration; prestudy bone scan completed within 12 weeks prior to registration and/or within 4 weeks prior to surgery

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No prior hormonal therapy (except for up to 14 days of tamoxifen stopped prior to registration) Prior estrogen- and/or progesterone-containing hormone preparations for nononcologic therapy allowed, but must be discontinued prior to registration Postmenopausal estrogen therapy should be discontinued in all patients at the time of diagnosis of breast cancer Radiotherapy: Postoperative chest wall and/or regional lymph node irradiation allowed for mastectomy patients (at discretion of the physician) either prior to registration or on protocol for any of the following: Tumor greater than 5 cm in diameter 4 or more positive nodes Extranodal extension of tumor into the axillary fat No radiotherapy for any other reason in mastectomy patients Postoperative radiotherapy either prior to registration, during tamoxifen, or after completion of chemotherapy required for lumpectomy patients Radiotherapy must be completed (if it is to be given before chemotherapy) prior to registration No immediate radiotherapy after randomization to chemotherapy Surgery: Radical, modified radical, or breast-sparing surgical procedure with at least a level I and II axillary dissection and analysis of at least 6 nodes required within 12 weeks prior to registration Lumpectomy must include: Total excisional biopsy with rim of normal breast tissue Microscopically negative margins Level I and II axillary dissection Tumor no more than 5 cm in greatest diameter Clinical and mammographic examination demonstrating absence of multicentric lesions Type of surgery, number of nodes examined, number of positive nodes, and size of the primary tumor (size of the largest tumor if more than 1 mass) must be recorded

Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00929591
CDR0000075692, U10CA032102, SWOG-8814, CAN-NCIC-MA9, CLB-9194, EST-4188, NCCTG-883051, INT-0100
Yes
Southwest Oncology Group
Southwest Oncology Group
  • National Cancer Institute (NCI)
  • Eastern Cooperative Oncology Group
  • North Central Cancer Treatment Group
  • Cancer and Leukemia Group B
  • NCIC Clinical Trials Group
Study Chair: Kathy S. Albain, MD Loyola University
Study Chair: Charles D. Cobau, MD Flower Hospital Cancer Center
Study Chair: James N. Ingle, MD Mayo Clinic
Study Chair: Ellis G. Levine, MD Roswell Park Cancer Institute
Study Chair: Kathleen I. Pritchard, MD Edmond Odette Cancer Centre at Sunnybrook
Southwest Oncology Group
January 2013

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