Erectile Dysfunction, CTCAE, Impotence, Male Erectile Disorder, Prostate Adenocarcinoma
Conditions
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.
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.
Interventions
DRUGAtorvastatin
Given PO
DRUGPentoxifylline
Given PO
DIETARY_SUPPLEMENTVitamin E Compound
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
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 * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in International Index of Erectile Function (IIEF) Scores | 12 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 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. |
| Choosing Other Erectile Dysfunction (ED) Treatments After Pentoxifylline, Atorvastatin and Vitamin E (PAVE) | Up to 12 months | To report the rate of choosing other ED treatments after PAVE. |
Countries
United States
Participant flow
Recruitment details
Recruitment Details: November 2019 to April of 2021. The recruitment of the participants occurred at the clinic and remotely via telephone calls.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants not on any statin and were started on Atorvastatin 10 mg 1 tab daily with addition of receiving Pentoxyfilline 400 mg 1 tab 3 times daily and Vitamin E 1000units 1 tab daily. | 5 |
| Cohort 2 Participants were on some amount of Atorvastatin and the dosage ramined the same With addition of receiving Pentoxyfilline 400 mg 1 tab 3 times daily and Vitamin E 1000units 1 tab daily. | 8 |
| Cohort 3 Participants on some other statin beside atorvastatin and the dosage remained the same with addition of receiving Pentoxyfilline 400 mg 1 tab 3 times daily and Vitamin E 1000units 1 tab daily. | 1 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 5 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 0 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 1 Participants | 11 Participants |
| Region of Enrollment United States | 5 participants | 8 participants | 1 participants | 14 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 1 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 8 | 0 / 1 |
| other Total, other adverse events | 0 / 5 | 2 / 8 | 0 / 1 |
| serious Total, serious adverse events | 0 / 5 | 0 / 8 | 0 / 1 |
Outcome results
Primary
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)
Time frame: 12 months
Population: The data shows that 0 participants achieved any clinically significant improvement.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Change in International Index of Erectile Function (IIEF) Scores | 0 Participants |
| Cohort 2 | Change in International Index of Erectile Function (IIEF) Scores | 0 Participants |
| Cohort 3 | Change in International Index of Erectile Function (IIEF) Scores | 0 Participants |
Secondary
Choosing Other Erectile Dysfunction (ED) Treatments After Pentoxifylline, Atorvastatin and Vitamin E (PAVE)
To report the rate of choosing other ED treatments after PAVE.
Time frame: Up to 12 months
Population: No participants on cohort 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Choosing Other Erectile Dysfunction (ED) Treatments After Pentoxifylline, Atorvastatin and Vitamin E (PAVE) | 1 Participants |
| Cohort 2 | Choosing Other Erectile Dysfunction (ED) Treatments After Pentoxifylline, Atorvastatin and Vitamin E (PAVE) | 0 Participants |
| Cohort 3 | Choosing Other Erectile Dysfunction (ED) Treatments After Pentoxifylline, Atorvastatin and Vitamin E (PAVE) | 0 Participants |
Secondary
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.
Time frame: Up to 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Incidence of Adverse Events (AEs) | Serious Adverse Event | 0 Participants |
| Cohort 1 | Number of Participants With Incidence of Adverse Events (AEs) | Adverse Event | 0 Participants |
| Cohort 2 | Number of Participants With Incidence of Adverse Events (AEs) | Serious Adverse Event | 0 Participants |
| Cohort 2 | Number of Participants With Incidence of Adverse Events (AEs) | Adverse Event | 2 Participants |
| Cohort 3 | Number of Participants With Incidence of Adverse Events (AEs) | Serious Adverse Event | 0 Participants |
| Cohort 3 | Number of Participants With Incidence of Adverse Events (AEs) | Adverse Event | 0 Participants |