Official Title: “This Protocol is a Randomized Prospective Study Comparing Prophylactic and on Demand Sildenafil Citrate Usage Administered During and After Radiotherapy With or Without Hormone Therapy Versus Radiotherapy With or Without Hormone Therapy Alone for the Preservation of Erectile Function After Therapy for Potent Patients With Clinically Localized Prostate Cancer”

Radiation sometimes affects the ability for a person to have a normal erection. Complete loss of erections after radiation treatment can happen in 40-50% of treated patients. There are medications, like sildenafil (also known as Viagra), that can help the ability to get back erections in almost 70% of such patients.

The purpose of this study is to see if taking Viagra every day starting right before, during and for about 6 months after treatment, could reduce the risk of long-term erectile dysfunction.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment

Study Primary Completion Date: February 2010

This protocol is a randomized prospective study comparing prophylactic and on demand Sildenafil Citrate usage administered during and after radiotherapy in combination with or without hormone therapy versus radiotherapy alone for the preservation of erectile function in potent patients with clinically localized prostate cancer. The primary objectives of this protocol are to determine if prophylactic and on demand usage of Sildenafil Citrate can preserve spontaneous erectile function as well as diminish the time to restoration of erectile function in potent men receiving radiotherapy with or without hormone therapy for localized prostate cancer. Secondary objectives of this study are: to determine whether prophylactic and on demand use of Sildenafil Citrate during therapy may improve the long-term response to the drug following treatment; to determine whether prophylactic and on demand use of Sildenafil Citrate during therapy will reduce acute and late urinary effects of radiotherapy; to determine the impact of dosimetry and radiation exposure to both the neurovascular bundle and bulb of the penis on erectile function preservation in the study population undergoing brachytherapy and hormone therapy; to asses the impact on quality of life following prophylactic and on demand Sildenafil Citrate usage in the study population; to determine the relationship between testosterone levels, erectile function and efficacy of prophylactic and on demand Sildenafil Citrate usage in the study population.

Intervention(s) in this Clinical Trial

• Drug: sildenafil citrate and questionaires
  • Hormone therapy patients will be instructed to begin the study drug simultaneously or within 1 month of start of hormone therapy. These patients will then continue to take the study drug for approximately 6 months following start of radiotherapy.In addition, during prophylactic phase (drug and placebo prophylactic arms) patients will have the opportunity to utilize oral 50 mg. tablets of Sildenafil Citrate in an on demand open label, flexible dose fashion. Hormone patients will be offered on demand Sildenafil for approximately 15-21 months. Hormone therapy patients will complete assessments at baseline (within 4 weeks of start of study treatment) each month (only IIEF and QOL) before start of radiotherapy, at start of radiotherapy and at months 3, 6, 9, 12 18 and 24 from start of radiotherapy. Testosterone assessments will take place at baseline, and months 12 and 24.
• Drug: placebo tablets and questionaires
  • Non-hormone therapy patients will be instructed to begin the study drug 3 days prior to start of radiotherapy. Patients beginning study drug anytime between 3 days before start of radiotherapy and 2 weeks after the first day of radiotherapy will also be acceptable. These patients will then continue to take the study drug for approximately 6 months following start of radiotherapy. In addition, during prophylactic phase (drug and placebo prophylactic arms) patients will have the opportunity to utilize oral 50 mg. tablets of Sildenafil Citrate in an on demand, open label, flexible dose fashion. Non-hormone patients will be offered on demand Sildenafil for approximately 12 months. Assessments (IIEF, IPSS, QOL) will be completed by non-hormone therapy patients at baseline (within 4 weeks of start of study treatment) and at approximately months 3, 6, 9, 12, 18 and 24 from start of radiotherapy. Testosterone assessments will take place at baseline, and months 12 and 24.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • radiotherapy with hormones, questionaire assessments
• Placebo Comparator: 2
  • radiotherapy without hormones, questionaire assessments

Primary Measures

• Determine if prophylactic sildenafil citrate used before, during & after course of radiotherapy (external beam radiotherapy &/or brachytherapy w or w/o hormone therapy) can prevent loss of spontaneous erectile function 2 yrs from start of radiation tx.
  • Time Frame: 2 years from start of RT
    Safety Issue?: No
• Diminish the time to restoration of erectile function for the study population.
  • Time Frame: 2 years
    Safety Issue?: No

Secondary Measures

• To determine if the prophylactic use of sildenafil citrate during radiotherapy may improve the long-term response to the drug following treatment
  • Time Frame: 2 years from start of RT
    Safety Issue?: No
• To determine if sildenafil citrate used during a course of external beam radiotherapy or brachytherapy among patients will reduce acute and late urinary effects of radiotherapy.
  • Time Frame: 2 years
    Safety Issue?: No
• To determine the impact of dosimetry and radiation exposure to both the neurovascular bundle and bulb of the penis on erectile function preservation in the study population undergoing brachytherapy.
  • Time Frame: 2 years
    Safety Issue?: No
• To assess the impact on quality of life following prophylactic and on demand Sildenafil utilization in the study population.
  • Time Frame: 2 years
    Safety Issue?: No
• To determine the relationship between testosterone levels, erectile function and efficacy of prophylactic and on demand Sildenafil utilization in the study population.
  • Time Frame: 2 years
    Safety Issue?: No

Inclusion Criteria:

• To receive external beam radiation therapy and/or brachytherapy for biopsy-proven prostate cancer.
• Baseline International Index of Erectile Function (IIEF) erectile function domain score >= 17.
• Patients receiving radiotherapy with hormone therapy undergoing a maximum of 9 months of hormone therapy will be acceptable.

Exclusion Criteria:

• Baseline IIEF-EF (1-30) domain score of <17 pre-therapy
• Current routine use of erectogenic agents (use of agents > 4 times per month would constitute "routine use")
• Neoadjuvant androgen deprivation therapy started more than 1 month prior to entry into study (intake of Bicalutamide alone does not constitute exclusion from study entry)
• Have a clinically significant penile deformity in the opinion of the investigator (ie:
• Peyronie's Disease)
• Non-organ confined disease
• Prior prostate surgery or cryotherapy
• Prior prostate radiotherapy started more than 2 weeks prior to entry into study
• Currently taking 2 Flomax
• Penile implant history
• Present at baseline with chronic angina requiring nitrates, angina occurring during sexual intercourse or unstable angina within the last 6 months.
• History of myocardial infarction, coronary artery bypass graft surgery or percutaneous coronary intervention within 90 days of baseline visit.
• History of significant cardiac conduction defect within 90 days of baseline visit.
• Exhibit systolic blood pressure > 170 or < 90 mm Hg or diastolic blood pressure > 100 or < 50 mm Hg at baseline visit or have a history of malignant hypertension
• Have any condition that would interfere with the subject's ability to provide informed consent or comply with study instructions, would place subject at increased risk, or might confound the interpretation of the study results
• Currently receive treatment with nitrates, cancer chemotherapy, or antiandrogens (except finasteride taken as Propecia or Proscar)
• Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Michael J Zelefsky, M.D. Principal Investigator Memorial Sloan-Kettering Cancer Center  

Overall Contact: Michael J. Zelefsky, M.D. 212-639-6802 zelefskm@mskcc.org

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00142506

Study ID Number: 05-007

ClinicalTrials.gov Identifier: NCT00142506

Health Authority: United States: Institutional Review Board

Memorial Sloan-Kettering Cancer Center