Study of Effectiveness of Lovastatin to Prevent Radiation-Induced Rectal Injury

Study Overview
=================
Brief Summary
-----------------
Lovastatin may protect against late effects of radiation therapy in patients with prostate cancer

Detailed Description
-----------------
Oral lovastatin will be given at the dose of 20 mg/day with evening meal beginning on the first day of external beam radiation therapy (external beam alone or external beam followed by brachytherapy) or on the first day of brachytherapy (brachytherapy alone or brachytherapy followed by external beam radiotherapy) and continue for 12 months.

Official Title
-----------------
A Phase II Study to Prevent Radiation-Induced Rectal Injury With Lovastatin

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: lovastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate Planned treatment with radiation therapy to include external beam and/or brachytherapy with curative intent (total dose ≥60 Gy). A portion of the rectum must receive at least 60 Gy. Age at least 18 years Karnofsky Performance Status (KPS) ≥ 70 No history of prior radiotherapy to the prostate or rectum History of prior malignancy, if likely to live at least 4 years, is acceptable. No evidence of distant metastases Patients may be taking an HMG-coA-reductase inhibitor, but to be eligible, they must be able to be changed to lovastatin 20 mg/day, with the permission of their prescribing physician. Creatine kinase < 5 times upper normal limit Sufficient renal function defined as calculated creatinine clearance ≥ 30ml/min transaminases < 3 times upper normal limit Exclusion Criteria: Planned abdomino-perineal resection after radiotherapy Contraindication to an HMG-coA-reductase inhibitor Major medical or psychiatric illness, which in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up. Currently taking an inhibitor of cytochrome P450 3A4 Active liver or muscle disease

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

Sexes Eligible for Study
-----------------
Male

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: Lovastatin for 1 yr<br>Lovastatin (20-80 mg/d) was started on day 1 of radiation and continued for 12 months. Patients were followed for an additional 12 months. Lovastatin once per day for 1 year. After the implant, they are asked to return for checkups (study visits 4-13) 4 weeks, 8 weeks, 4 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months and 24 months after the procedure. At 8 weeks, 4 months, 6 months, 9 months and 12 months, will also have a blood test to check their liver. | Drug: lovastatin<br>* The HMG-coA reductase inhibitor used in this study will be lovastatin. Dosage: 20 mg/d PO with evening meal. Patients on a higher dose of lovastatin at the time of study entry may continue at that dose level; for patients switching to lovastatin, the dose will be at the discretion of the prescribing physician, but must be at least 20 mg/day.Schedule: begin on the first day of external beam radiation therapy (external beam alone or external beam followed by brachytherapy) or on the day of brachytherapy (brachytherapy alone or brachytherapy followed by external beam radiotherapy) and continue for 12 months. Patients or their third party payers will be expected to cover the cost of the drug.<br>* Other names: Mevacor;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Physician Reported Rectal Toxicity ≥ Grade 2 During the First 2 Years of Radiation Treatment | The primary endpoint of this study was percentage of participants with physician reported rectal toxicity ≥Grade 2 during the first 2 years after treatment. A one sided test will be conducted in order to evaluate reduction of risk from adding Lovastatin. The analysis is using a one-stage design, 5% level of significance, and 83% power. | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prostate cancer, radiation therapy, lovastatin, rectal injury