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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Adenocarcinoma; Male Erectile Disorder; Impotence; Erectile Dysfunction, CTCAE
• Intervention / Treatment: Drug: Atorvastatin; Drug: Pentoxifylline; Dietary supplement: Vitamin E Compound

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Trental; PTX; Oxpentifylline; Pentoxyphylline; Dietary supplement: Vitamin E Compound; Given PO; Other Names: Vitamin E; 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-ol; E Vitamin

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline patient features	Exploratory analyses will be utilized to determine whether baseline patient features can predict response to PAVE or adverse events.	Baseline

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Chad Tang, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): November 2, 2022

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Erectile Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antimetabolites; Protective Agents; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Atorvastatin; Vitamin E; Tocopherols; alpha-Tocopherol; Vitamins; Tocotrienols; Pentoxifylline
• Other Study ID Numbers: 2018-0785 (Other Identifier: M D Anderson Cancer Center); NCI-2019-00235 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No