Pentoxifylline, Atorvastatin, and Vitamin E in Treating Patients With Erectile Dysfunction After Radiation Therapy for Prostate Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well pentoxifylline, atorvastatin, and vitamin E (PAVE) work in treating patients with erectile dysfunction after radiation therapy for prostate cancer. Atorvastatin may reduce high cholesterol. Pentoxifylline and vitamin E may enhance blood flow. Giving PAVE may work better in treating prostate cancer patients with post-radiation therapy erectile dysfunction.

Detailed Description
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PRIMARY OBJECTIVE: I. To estimate the proportion of patients who achieve a clinically significant improvement in erectile dysfunction (ED) when treated with a combination of atorvastatin or patient's currently prescribed statin, vitamin E, and pentoxifylline (PAVE). SECONDARY OBJECTIVES: I. To report the safety profile of PAVE. II. To report the rate of choosing other ED treatments after PAVE. OUTLINE: Patients receive atorvastatin orally (PO) once daily (QD) for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Beginning week 7, patients receive atorvastatin PO QD, vitamin E PO QD, and pentoxifylline PO thrice daily (TID) for up to 12 months in the absence of disease progression or unacceptable toxicity.

Official Title
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Pentoxifylline, Atorvastatin, and Vitamin E (PAVE) as Treatment for Radiation-Induced Erectile Dysfunction

Conditions
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Male Erectile Disorder, Prostate Adenocarcinoma, Erectile Dysfunction, CTCAE, Impotence

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Pentoxifylline
* Dietary Supplement: Vitamin E Compound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate Previous radiation therapy (any form) with curative intent for prostate cancer Erectile dysfunction, as determined by an International Index of Erectile Function (IIEF)-5 score of < 22 Normal testosterone (including men on testosterone replacement), defined as testosterone > 150 ng/dl at the time of screening Karnofsky Performance Status (KPS) >= 70, or Eastern Cooperative Oncology Group (ECOG) 0-2 Patients may be taking an HMG-coA-reductase inhibitor Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 X upper limits of normal (ULN) Creatinine kinase < 5 times ULN Normal renal function is defined as creatinine clearance >= 30 ml/min via the Cockcroft Gault formula Exclusion Criteria: No androgen deprivation therapy within the past 12 months No contraindication to an HMG-coA-reductase inhibitor, vitamin E or pentoxifylline Not currently taking cyclosporine, the human immunodeficiency virus (HIV) protease inhibitors, hepatitis C protease inhibitors, gemfibrozil, other fibrates, clarithromycin, itraconazole or strong inhibitors of CYP3A4 No recent cerebral or retinal hemorrhage that in the opinion of the treating physician would make PAVE unsafe (within 6 months) No current chemotherapy during study participation No active liver or muscle disease that in the opinion of the treating physician would make PAVE unsafe No prior radical prostatectomy, cystoprostatectomy, abdominoperineal resection or retroperitoneal lymph node dissection Not currently taking a 5PDE inhibitor nor have used one within 30 days of enrolling in the study No recent deep venous thrombosis, myocardial infarction or pulmonary embolism (within 6 months) requiring continued anticoagulation other than aspirin (acetylsalicylic acid [ASA]) No cardiac arrhythmias or artificial heart valves requiring anticoagulation other than ASA No concurrent drugs with anti-platelet therapy properties (e.g., P2Y12 inhibitors, non-steroidal anti-inflammatory agents, selective serotonin reuptake inhibitors) other than low dose ASA (81 mg/d) Not currently taking high dose statin therapy, defined as rosuvastatin > 10 mg/d or atorvastatin > 40 mg/d Not currently taking theophylline No history of active peptic ulcer disease in the past 6 months No history of intolerance to pentoxifylline or methylxanthines such as caffeine, theophylline and theobromine that in the opinion of the treating physician would make PAVE unsafe No concurrent use of CYP1A2 inhibitors (e.g., ciprofloxacin), ketorolac, or vitamin K antagonists (e.g. warfarin)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (atorvastatin, vitamin E, pentoxifylline)<br>Patients receive atorvastatin PO QD for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Beginning week 7, patients receive atorvastatin PO QD, vitamin E PO QD, and pentoxifylline PO TID for up to 12 months in the absence of disease progression or unacceptable toxicity. | Drug: Atorvastatin<br>* Given PO<br>Drug: Pentoxifylline<br>* Given PO<br>* Other names: Trental;Dietary Supplement: Vitamin E Compound<br>* Given PO<br>* Other names: Vitamin E;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in International Index of Erectile Function (IIEF) Scores | To estimate the proportion of participants who achieve a clinically significant improvement in erectile dysfunction (ED) when treated with a combination of Atorvastatin or participant's currently prescribed statin, Vitamin E, and Pentoxifylline (PAVE) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Incidence of Adverse Events (AEs) | The safety profile of the pentoxifylline, atorvastatin and vitamin E (PAVE) combination will be reported for each cohort, with adverse events summarized by grade and time to onset to first grade 3 adverse event. | Up to 12 months | 
| Choosing Other Erectile Dysfunction (ED) Treatments After Pentoxifylline, Atorvastatin and Vitamin E (PAVE) | To report the rate of choosing other ED treatments after PAVE. | Up to 12 months |