Lovastatin in Reducing Side Effects After Radiation Therapy in Women With Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs, such as lovastatin, may protect normal cells from the side effects of radiation therapy. PURPOSE: This phase II trial is studying how well lovastatin works in reducing side effects after radiation therapy in women with breast cancer.

Detailed Description
-----------------
OBJECTIVES: To determine the incidence of good/excellent cosmetic outcome, as defined by the Harvard Scale, after radiotherapy in women treated with lovastatin, as compared to historical controls. OUTLINE: Patients undergo standard external beam whole-breast irradiation and/or accelerated partial breast irradiation. Patients receive oral lovastatin once daily beginning on the first day of radiotherapy and continuing for 12 months in the absence of disease progression or unacceptable toxicity. Patients complete a questionnaire, the Breast Cancer Treatment Outcome Scale, at baseline and then at 6 months, 12 months, and 3 years after completion of radiotherapy to assess cosmetic and functional outcomes. After completion of radiotherapy, patients are followed periodically for up to 5 years.

Official Title
-----------------
A Phase II Study Using Lovastatin to Improve Cosmetic Outcome After Radiation Therapy for Breast Cancer

Conditions
-----------------
Breast Cancer, Radiation Toxicity

Intervention / Treatment
-----------------
* Drug: lovastatin
* Other: questionnaire administration
* Procedure: adjuvant therapy
* Radiation: accelerated partial breast irradiation
* Radiation: external beam radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of invasive or in situ epithelial cancer of the breast Stage 0, I, or II (Tis, T1, or T2) disease Unifocal disease (single focus that can be encompassed by breast-conserving surgery) Has undergone prior surgical resection of the primary lesion (lumpectomy) and axillary nodal evaluation (if invasive disease is present) Negative surgical margins (≥ 1 mm) Planning to undergo radiotherapy with either standard external beam radiotherapy or accelerated partial breast irradiation (interstitial or balloon brachytherapy) No Paget disease of the nipple No evidence of distant metastases Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Karnofsky performance status 70-100% Transaminases < 3 times upper limit of normal (ULN) Creatine kinase < 5 times ULN Creatinine clearance ≥ 30 mL/min Negative pregnancy test No active liver or muscle disease No history of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma, or dermatomyositis) History of prior malignancy allowed provided life expectancy is ≥ 4 years No major medical or psychiatric illness that, in the investigator's opinion, would prevent completion of study treatment or interfere with follow-up No contraindication to an HMG-coA-reductase inhibitor PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior radiotherapy to the breast, lung, or mediastinum Prior radiotherapy to the contralateral breast allowed No chemotherapy for ≥ 2 weeks prior to, during, and for ≥ 2 weeks after completion of radiotherapy No concurrent cytochrome P450 3A4 inhibitors Concurrent HMG-coA-reductase inhibitor allowed provided patient is able to switch to 20 mg of lovastatin per day Concurrent tamoxifen or an aromatase inhibitor allowed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive care (lovastatin)<br>Patients undergo 25-28 fractions of standard whole-breast irradiation followed by a boost to the tumor bed or 10 fractions of accelerated partial-breast irradiation with balloon brachytherapy BID over 5-10 days. Patients also receive lovastatin PO QD for 12 months beginning on day 1 of radiation therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | Drug: lovastatin<br> <br> Other: questionnaire administration<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: accelerated partial breast irradiation<br> <br> Radiation: external beam radiation therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Good/Excellent Cosmetic Outcome During the First 5 Years After Radiotherapy | Proportion of good or excellent cosmetic outcomes, assessed using the Harvard Cosmesis Scale | during the first 5 years after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
radiation toxicity, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, breast cancer in situ