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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03830164

Collaborator

National Cancer Institute (NCI) (NIH)

270

Enrollment

Location

Arm

33.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Male Erectile Disorder Prostate Adenocarcinoma Erectile Dysfunction, CTCAE Impotence	Drug: Atorvastatin Drug: Pentoxifylline Dietary Supplement: Vitamin E Compound	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

270 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 20, 2019

Anticipated Primary Completion Date :

Sep 17, 2022

Anticipated Study Completion Date :

Sep 17, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (atorvastatin, vitamin E, pentoxifylline) 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 Given PO Drug: Pentoxifylline Given PO Other Names: Oxpentifylline Pentoxyphylline PTX Trental Dietary Supplement: Vitamin E Compound Given PO Other Names: 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol E Vitamin Vitamin E

Arm

Intervention/Treatment

Experimental: Treatment (atorvastatin, vitamin E, pentoxifylline)

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

Given PO

Drug: Pentoxifylline

Given PO

Other Names:

Oxpentifylline

Pentoxyphylline

PTX

Trental

Dietary Supplement: Vitamin E Compound

Given PO

Other Names:

2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol

E Vitamin

Vitamin E

Outcome Measures

Primary Outcome Measures

Change in International Index of Erectile Function (IIEF) scores [Baseline up to 12 months]
Patients' baseline erectile dysfunction (ED) levels will be reported along with the proportion for patients who improve by at least 1 level according to the IIEF for each time point measured. The proportion will be reported along with a 95% credible interval implementing a non-informative prior of beta (0.33, 0.67). Additionally, the proportion of patients who ever improve by at least 1 level will be reported overall.

Secondary Outcome Measures

Incidence of adverse events (AEs) [Up to 12 months]
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.
Rate of choosing other ED treatments after PAVE [Up to 12 months]
The number of patients who drop out of the study to start an ED prescription medication will be reported.

Other Outcome Measures

Baseline patient features [Baseline]
Exploratory analyses will be utilized to determine whether baseline patient features can predict response to PAVE or adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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)