Adjuvant Chemotherapy in Treating Women Who Have Undergone Resection for Relapsed Breast Cancer; Chemotherapy as Adjuvant for LOcally Recurrent Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether chemotherapy is effective in treating women who have undergone surgery and radiation therapy for relapsed breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of adjuvant chemotherapy in treating women who have undergone resection for local and/or regional relapsed breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of adjuvant chemotherapy, in terms of disease-free survival, in women with radically resected loco-regional relapsed breast cancer. Secondary Determine the systemic disease-free and overall survival of patients treated with this regimen. Determine the sites of recurrence, incidence of second (non-breast) malignancies, and causes of death without relapse of breast cancer in patients treated with this regimen. Determine the quality of life of patients treated with this regimen (QOL portion closed 11/13/08). OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior chemotherapy (yes vs no), estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (yes vs no), and location of recurrence (breast vs mastectomy scar/chest wall vs regional lymph nodes). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive radiotherapy* within 6 months after surgery. Arm II: Within 10 weeks after surgery, patients receive at least 3 courses of an adjuvant chemotherapy regimen as determined by the investigator. Patients also receive radiotherapy* within 6 months after surgery and after the completion of chemotherapy OR integrated with chemotherapy. NOTE: *Patients with clear margins (R0) who received prior adjuvant radiotherapy are not required to receive further radiotherapy Patients with ER and/or PR positive tumors also receive standard hormonal therapy. Quality of life is assessed at baseline and at 9 and 12 months (QOL portion closed 11/13/08). Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 265 patients will be accrued for this study within 4 years.

Official Title
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A Randomized Clinical Trial Of Adjuvant Chemotherapy For Radically Resected Loco-Regional Relapse Of Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: chemotherapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast cancer First local and/or regional (i.e., ipsilateral axillary or internal mammary lymph node region) recurrence after primary treatment with mastectomy or lumpectomy/quadrantectomy with clear surgical margins Local failure is defined as a tumor recurrence in any soft tissue of the ipsilateral conserved breast or the chest wall, mastectomy scar, and/or skin Regional failure is defined as a tumor recurrence in the ipsilateral axillary lymph nodes, extranodal soft tissue of the ipsilateral axilla, and/or ipsilateral internal mammary. Regional failure does not include supraclavicular lymph nodes or tumor in the opposite breast No other prior recurrence in any site, including local Surgical resection of the recurrence meeting 1 of the following criteria: Uninvolved (clear) margins and planned radiotherapy with at least 40 Gy for patients who had no prior adjuvant radiotherapy Mastectomy of the recurrence with uninvolved (clear) margins after lumpectomy/quadrantectomy alone for the primary Adjuvant trastuzumab (Herceptin®) therapy or other HER-2 directed therapies are allowed for patients with HER-2 positive tumors and must be declared prior to randomization No evidence of distant metastasis, including ipsilateral supraclavicular lymph nodes, by x-ray or CT scan of the chest, ultrasound or CT scan of the abdomen and pelvis, or bone scintigraphy only if alkaline phosphatase is > 2 times normal or if medically indicated (e.g., bone pain) No macroscopically incomplete surgery No bilateral malignancy except carcinoma in situ No suspicious mass in the opposite breast unless that mass has been proven by biopsy to be benign No skeletal pain of unknown cause No hot spots on bone scan for which metastases cannot be ruled out by x-ray, MRI, and/or CT scan Hormone receptor status: Determined in the recurrent tumor by immunohistochemistry and/or ligand-binding assay Estrogen receptor positive or negative Progesterone receptor positive or negative PATIENT CHARACTERISTICS: Age Minimum 18 years Sex Female Menopausal status Not specified Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic No elevated alkaline phosphatase Renal Not specified Other Fertile patients must use effective non-hormonal contraception Medically suitable for chemotherapy of 3-6 months duration No other primary malignant tumors except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer No non-malignant systemic disease that would preclude study treatment or prolong follow-up No psychiatric or addictive disorder that would preclude giving informed consent No history of noncompliance to medical regimens or potential for being unreliable PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy See Disease Characteristics Surgery See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive radiotherapy* within 6 months after surgery. | Radiation: radiation therapy<br>* Given within 6 months after surgery<br>|
| Experimental: Arm II<br>Within 10 weeks after surgery, patients receive at least 3 courses of an adjuvant chemotherapy regimen as determined by the investigator. Patients may receive radiotherapy within 6 months after surgery and after the completion of chemotherapy OR integrated with chemotherapy. | Drug: chemotherapy<br>* Given within 10 weeks after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival |  | 5 years after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 5 years after randomization | 
| Sites of First Failures | Tumor recurrence in the breast, lymph nodes or other areas of the body including bone, lung, liver, central nervous system, bone marrow | 5 years after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer