Prostate Cancer
Conditions
Keywords
prostate cancer, radiation therapy, lovastatin, rectal injury
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.
Interventions
DRUGlovastatin
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.
Sponsors
Hunter Holmes Mcguire Veteran Affairs Medical Center
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Physician Reported Rectal Toxicity ≥ Grade 2 During the First 2 Years of Radiation Treatment | 24 months | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment period was between between 2007 to 2013 at Virginia Commonwealth University, Stony Point, Hanover Medical Center, Southside Regional Medical Center, and Hunter Holmes McGuire Veterans Affairs Medical Center (VAMC).
Pre-assignment details
Enrollment period was between April 12, 2007 and May 30, 2013. During that time 73 consecutive subjects enrolled in the study, 72 started treatment. A total of 20 subjects were ineligible for analysis because they did not reach 6 months of Lovastatin treatment, resulting in a total of 53 evaluable subjects.
Participants by arm
| Arm | Count |
|---|---|
| Supportive Care (Lovastatin) (Evaluable) The 53 subjects started Lovastatin treatment on the first day of radiation (either EBRT,external beam radiotherapy, or on the day of brachytherapy) and continued up to 12 months. The subjects were considered evaluable for analysis because they completed 6 months of Lovastatin. | 53 |
| Supportive Care (Lovastatin) (Ineligible) The 20 subjects started Lovastatin on the first day of radiation (either EBRT,external beam radiotherapy, or on the day of brachytherapy). The subjects were ineligible because they did not complete 6 months of Lovastatin. | 20 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Pre-treatment | Non-compliance | 1 |
| Treatment (Lovastatin) | Death | 1 |
| Treatment (Lovastatin) | Development of metastatic second primary | 1 |
| Treatment (Lovastatin) | Intolerance of Lovastatin | 7 |
| Treatment (Lovastatin) | Non-compliance | 6 |
| Treatment (Lovastatin) | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Supportive Care (Lovastatin) (Evaluable) | Total | Supportive Care (Lovastatin) (Ineligible) |
|---|---|---|---|
| Age, Continuous | 63 years | 62 years | 58.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 32 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 41 Participants | 10 Participants |
| Region of Enrollment United States | 53 participants | 73 participants | 20 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 53 Participants | 73 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 70 / 72 |
| serious Total, serious adverse events | 8 / 72 |
Outcome results
Primary
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.
Time frame: 24 months
Population: The primary endpoint of the study was percentage of participants with physician reported rectal toxicity ≥Grade 2 during the first 2 years after treatment. Only the highest-grade toxicity for each symptom was counted. Symptoms starting in the acute period and unresolved beyond 90 days post treatment are considered late toxicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Supportive Care (Lovastatin) (Evaluable) | Percentage of Participants With Physician Reported Rectal Toxicity ≥ Grade 2 During the First 2 Years of Radiation Treatment | 38 percentage of participants |
p-value: 0.9138t-test, 1 sided