Radiation Therapy to the Head in Preventing Brain Metastases in Women Receiving Trastuzumab and Chemotherapy for Metastatic or Locally Advanced Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy directed at the head is effective in preventing brain metastases in patients with advanced cancer. PURPOSE: This randomized phase III trial is studying radiation therapy to the head to see how well it works in preventing brain metastases in women receiving trastuzumab and chemotherapy for metastatic or locally advanced breast cancer.

Detailed Description
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OBJECTIVES: To test if prophylactic cranial radiotherapy delivering 30 Gy in 10 fractions will significantly reduce (from 35% to 21% at 2 years) the incidence of symptomatic brain metastases in patients treated with trastuzumab (Herceptin®) for metastatic breast cancer. OUTLINE: This is a multicenter study. Patients are stratified by center, type of systemic therapy (trastuzumab [Herceptin®] monotherapy vs combination with chemotherapy), hormone receptor status, and presence of lung metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive taxane/trastuzumab therapy for 6 weeks. While continuing taxane/trastuzumab therapy, patients then undergo 10 fractions of concurrent prophylactic cranial radiotherapy in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive taxane/trastuzumab therapy without concurrent prophylactic cranial radiotherapy. All patients undergo quality of life assessments every 8 weeks for 9 months. After completion of study treatment, patients are followed periodically for at least 1 year.

Official Title
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Prospective Randomised Clinical Trial Testing the Role of Prophylactic Cranial Radiotherapy in Patients Treated With Trastuzumab (Herceptin®) for Metastatic Breast Cancer

Conditions
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Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven breast carcinoma Metastatic or locally advanced disease Must demonstrate HER2 3+ positivity on IHC or 2+ over-expression and FISH test demonstrating C-erB2 gene amplification No known or suspected brain metastases or CNS disease, as defined by the presence of any of the following key symptoms: Headache Nausea and/or vomiting Clinical signs of raised intracranial pressure Seizures Focal symptoms Cognitive dysfunction Affective disorder Hormone receptor status not specified PATIENT CHARACTERISTICS: Female Postmenopausal status not specified ECOG performance status 0 or 1 Patients must a-priori be suitable for trastuzumab (Herceptin®) +/- chemotherapy in terms of bone marrow, hepatic, and renal function No prior history of cerebrovascular disease or neurological disorder including seizures PRIOR CONCURRENT THERAPY: No prior cranial radiotherapy No prior neurosurgery

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: trastuzumab|nan|
|Drug: chemotherapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of symptomatic brain metastases |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  |  | 
| Cerebral toxicity and quality of life |  |  | 

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