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Tadalafil in Preventing Erectile Dysfunction in Patients With Prostate Cancer Treated With Radiation Therapy

Primary Purpose

Prostate Cancer, Sexual Dysfunction

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Tadalafil

Placebo

About this trial

This is an interventional supportive care trial for Prostate Cancer focused on measuring sexual dysfunction, stage IIB prostate cancer, stage IIA prostate cancer, adenocarcinoma of the prostate

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Clinical stage T1b-T2b (AJCC, 6th ed.) adenocarcinoma of the prostate within 6 months of registration
Clinically negative lymph nodes as established by imaging (pelvic ± abdominal CT or MR), nodal sampling, or dissection within 3 months prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.5 cm. Lymph node assessment is optional, and at investigator discretion, for patients with Gleason Score <7.
No evidence of bone metastases (M0) on bone scan within 3 months prior to registration. Equivocal bone scan findings are allowed if plain films are negative for metastasis. Bone metastases assessment is optional, and at investigator discretion, for patients with Gleason Score <7.
Baseline serum prostatic specific antigen (PSA) value performed with an FDA-approved assay (e.g., Abbott, Hybritech) within 3 months prior to registration.
-4.1 Any of the following combinations of factors (NOTE: tumor found in 1 or both lobes on biopsy, but not palpable, will not alter T stage):
- T1b-T2b disease, Gleason Score <7 and serum total PSA that is <20 ng/ml or
- T1b-T2b disease, Gleason Score ≥7 and PSA that is <15 ng/ml
Serum total testosterone level prior to the initiation of radiation therapy (RT) within normal range according to institutional guidelines
Zubrod Performance Status 0 or 1 (Appendix III)
Age ≥ 18 years
Treatment that will consist of either external beam RT alone to the prostate ± seminal vesicles only at a dose between 75 Gy and 79.2 Gy or brachytherapy alone (NOTE: treatment with combined external RT and brachytherapy excludes patient participation)
Pretreatment (before starting prostate cancer treatment) erectile function as measured by IIEF Question 1, "How often were you able to get an erection during sexual activity?" - with responses of:
- "sometimes (about half the time)" [response 3] or
- "most times (much more than half the time)" [response 4] or
- "almost always/always" [response 5]
History of prior tadalafil use: Document usual dosage per sexual encounter, date of last dose, and patient's response (No; Yes-Unsatisfactory Response; Yes-Satisfactory Response). Regardless of past experience, the patient is eligible if he agrees to adhere to protocol and take only tadalafil or placebo prescribed on study.
Although patients with partners are targeted for recruitment, patients without partners or without partners willing to participate are eligible. Patients (and spouses/partners, if willing to participate) must be able to provide study-specific informed consent.

Exclusion Criteria:

The patient's participation in another medical research study that involves the treatment of ED
Previous or concomitant invasive cancer (American Joint Committee on Cancer [AJCC] Stage >0), other than localized basal cell or squamous cell skin carcinoma (AJCC Stage 0-II), or a hematological malignancy (e.g., leukemia, lymphoma, myeloma) unless continually disease free for at least 5 years
History of myocardial infarction within the last year
Heart failure in the last 6 months
Uncontrolled arrhythmias, hypotension (<90/50mm Hg), or uncontrolled hypertension (>170/100 mm Hg)
Stroke within the last 6 months
Use of luteinizing hormone-releasing hormone (LHRH) agonist androgen suppression (e.g., Lupron, Zoladex), anti-androgen (e.g., Casodex, Eulexin, Nilandron), or estrogenic (e.g., diethylstilbestrol) agents within the last 6 months
Current use of any organic nitrate or as needed nitrates (e.g., use of nitroglycerin)
Current use of cimetidine, ketoconazole, itraconazole, erythromycin, or ritonavir
Known moderate to severe renal insufficiency or end-stage renal disease
Known severe hepatic impairment
Use of mechanical (vacuum) devices, intracorporeal, intraurethral, topical, or oral (sildenafil, tadalafil, vardenafil) agents as therapy for ED or supplements to enhance sexual function within 5-7 days prior to the start of RT. Patients who discontinue these therapies remain eligible if they can meet eligibility criteria
Pretreatment (before starting prostate cancer treatment) ED as measured by IIEF Question 1, "How often were you able to get an erection during sexual activity?" - with responses of:
- "no sexual activity" [response 0] or
- "almost never/never" [response 1] or
- "a few times (much less than half the time)" [response 2]
Prior penile implant or history of bilateral orchiectomy
Prior prostatectomy, prostatic cryosurgery or high-intensity focused ultrasound (HIFU), radionuclide prostate brachytherapy, or chemotherapy for prostate cancer
Prior or anticipated combined external RT and brachytherapy
Prior or anticipated external RT to the pelvic ± para-aortic lymph nodes
Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.
Anatomical genital abnormalities or concurrent conditions that in the estimation of the physician would prohibit sexual intercourse or prevent study completion
Major medical or psychiatric illness which, in the opinion of the investigator, would prevent completion of treatment or would interfere with follow-up

Sites / Locations

University of Alabama at Birmingham
Providence Hospital
Arizona Center for Cancer Care-Peoria
Mayo Clinic in Arizona
Arizona Oncology Services Foundation
Arizona Oncology Associates-West Orange Grove
Sutter Cancer Centers Radiation Oncology Services-Auburn
Alta Bates Summit Medical Center-Herrick Campus
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Mercy San Juan Medical Center
Enloe Medical Center
Saint Agnes Medical Center
Veterans Administration Long Beach Medical Center
Northridge Hospital Medical Center
Kaiser Permanente Oakland-Broadway
Sutter Cancer Centers Radiation Oncology Services-Roseville
Radiological Associates of Sacramento
Mercy General Hospital Radiation Oncology Center
UCSF-Mount Zion
California Pacific Medical Center
Kaiser Permanente Cancer Treatment Center
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Sutter Solano Medical Center
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Penrose-Saint Francis Healthcare
The Hospital of Central Connecticut
Christiana Care Health System-Christiana Hospital
Washington Hospital Center
Broward Health North
University of Florida
Cancer Specialists of North Florida-Beaches
Baptist Cancer Institute
Cancer Specialists of North Florida-Southside
University of Florida Health Science Center
Mayo Clinic in Florida
Cancer Specialists of North Florida-Baptist South
University of Miami Miller School of Medicine-Sylvester Cancer Center
21st Century Oncology-Orange Park
21st Century Oncology-Palatka
Cancer Specialists of North Florida-Saint Augustine
John B Amos Cancer Center
Atlanta VA Medical Center
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Queen's Medical Center
University of Hawaii Cancer Center
The Cancer Center of Hawaii-Liliha
Saint Alphonsus Cancer Care Center-Boise
Advocate Illinois Masonic Medical Center
Advocate Lutheran General Hospital.
Saint John's Hospital
Carle Cancer Center
Saint Vincent Anderson Regional Hospital/Cancer Center
IU Health Bloomington
Radiation Oncology Associates PC
Parkview Hospital Randallia
IU Health Goshen Center for Cancer Care
Memorial Hospital of South Bend
Northern Indiana Cancer Research Consortium
Baptist Health Lexington
Mary Bird Perkins Cancer Center
Ochsner Clinic CCOP
Central Maine Medical Center
Maine Medical Center- Scarborough Campus
University of Maryland/Greenebaum Cancer Center
Saint Agnes Hospital
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Central Maryland Radiation Oncology in Howard County
Tate Cancer Center
Saint Anne's Hospital
Cape Cod Hospital
Bronson Battle Creek
Huron Valley-Sinai Hospital
Wayne State University/Karmanos Cancer Institute
Henry Ford Hospital
Saint John Hospital and Medical Center
McLaren-Flint
Mercy Health Saint Mary's
Spectrum Health at Butterworth Campus
West Michigan Cancer Center
William Beaumont Hospital-Royal Oak
Saint Mary's of Michigan
Saint Luke's Hospital of Duluth
Mayo Clinic
Coborn Cancer Center at Saint Cloud Hospital
United Hospital
Washington University School of Medicine
Barnes-Jewish West County Hospital
Siteman Cancer Center - Saint Peters
Good Samaritan Hospital
Saint Elizabeth Regional Medical Center
Nebraska Methodist Hospital
Concord Hospital
Wentworth-Douglass Hospital
Exeter Hospital
Elliot Hospital
Cooper Hospital University Medical Center
MD Anderson Cancer Center at Cooper-Voorhees
University of New Mexico Cancer Center
Memorial Medical Center - Las Cruces
New York Oncology Hematology PC - Albany
Southside Hospital
Lourdes Hospital
Veteran Affairs New York Harbor Healthcare System-Brooklyn Campus
Roswell Park Cancer Institute
Long Island Jewish Medical Center
Columbia University Medical Center
Mission Hospital-Memorial Campus
Duke University Medical Center
High Point Regional Hospital
The Coleman Radiation Center-Carteret General Hospital
CarolinaEast Health System-Medical Center
South Atlantic Radiation Oncology
Coastal Carolina Radiation Oncology
New Hanover Regional Medical Center
Summa Akron City Hospital/Cooper Cancer Center
Summa Barberton Hospital
University of Cincinnati
Case Western Reserve University
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland Clinic Foundation
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Ohio State University Medical Center
Cleveland Clinic Cancer Center Independence
Toledo Clinic Cancer Centers-Maumee
Hillcrest Hospital Cancer Center
Lake University Ireland Cancer Center
Southwest General Health Center Ireland Cancer Center
UHHS-Chagrin Highlands Medical Center
Cancer Care Center, Incorporated
Flower Hospital
UHHS-Westlake Medical Center
Cancer Treatment Center
Cleveland Clinic Wooster Specialty Center
University of Oklahoma Health Sciences Center
Clackamas Radiation Oncology Center
Willamette Valley Cancer Center
Three Rivers Community Hospital
Providence Medford Medical Center
Rogue Valley Medical Center
Providence Portland Medical Center
Western Oncology Research Consortium
Providence Saint Vincent Medical Center
Abington Memorial Hospital
Bryn Mawr Hospital
Delaware County Memorial Hospital
Fox Chase Cancer Center Buckingham
Adams Cancer Center
Cherry Tree Cancer Center
Academic Urology Prostate Center
Fox Chase Cancer Center
Albert Einstein Medical Center
Lankenau Medical Center
WellSpan Health-York Hospital
Spartanburg Regional Medical Center
Rapid City Regional Hospital
Texas Oncology-Denton South
The Klabzuba Cancer Center
University of Texas Medical Branch at Galveston
West Texas Cancer Center
University of Texas Health Science Center
Texas Cancer Center-Sherman
Texas Oncology Cancer Center Sugar Land
Tyler Cancer Center
Intermountain Medical Center
Utah Valley Regional Medical Center
Dixie Medical Center Regional Cancer Center
Utah Cancer Specialists-Salt Lake City
Huntsman Cancer Institute/University of Utah
University of Virginia
Danville Regional Medical Center
Virginia Mason CCOP
Compass Oncology Vancouver
Appleton Medical Center
Saint Vincent Hospital
Gundersen Lutheran
Mayo Clinic Health System-Franciscan Healthcare
Bay Area Medical Center
Aurora Saint Luke's Medical Center
Clement J. Zablocki VA Medical Center
Oconomowoc Memorial Hospital-ProHealth Care Inc
Door County Cancer Center
Waukesha Memorial Hospital - ProHealth Care
Aurora West Allis Medical Center
Tom Baker Cancer Centre
Cross Cancer Institute
BCCA-Cancer Centre for the Southern Interior
BCCA-Fraser Valley Cancer Centre
BCCA-Vancouver Cancer Centre
Juravinski Cancer Centre at Hamilton Health Sciences
London Regional Cancer Program
CHUQ - Pavilion Hotel-Dieu de Quebec
Allan Blair Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tadalafil

Placebo

Arm Description

Tadalafil

Placebo

Outcomes

Primary Outcome Measures

Percentage of Patients Maintaining Spontaneous (Off-drug) Erectile Function (EF) at Weeks 28-30 After Initiation of Radiation Therapy (RT)

EF is measured by Question 1 of the International Index of Erectile Function (IIEF). The IIEF is a validated 15-item for measuring patient-reported erectile function. Question 1 asks "How often were you able to get an erection during sexual activity?" Responses ranged from 0=no sexual activity, to 5=Almost always or always. Higher scores indicated better functioning. All patients have erectile function prior to initiation of RT, indicated by a score of 3, 4, or 5 on IIEF Q1. Patients with a lower IIEF Q1 score at weeks 28-30 than at baseline will have less erectile function and be categorized as nonresponders. Patients with similar or improved erectile function will be categorized as responders (maintaining). Patient-related predictors of at erectile function at this time point are also reported with this outcome measure.

Secondary Outcome Measures

Percentage of Patients Maintaining Spontaneous (Off-drug) EF at Years 1 and 2 After Initiation of RT

The International Index of Erectile Function (IIEF) is a validated 15-item for measuring patient-reported erectile function. Question 1 asks "How often were you able to get an erection during sexual activity?" Responses ranged from 0=no sexual activity, to 5=Almost always or always. Higher scores indicated better functioning. All patients have erectile function prior to initiation of RT, indicated by a score of 3, 4, or 5. Patients with a lower IIEF Q1 score at weeks 28-30 than at baseline will have less erectile function and be categorized as nonresponders. Patients with similar or improved erectile function will be categorized as responders (maintaining). Patient-related predictors of at erectile function at Years 1 and 2 are also reported with this outcome measure.

Overall Sexual Function as Measured by Change From Baseline in the International Index of Erectile Function (IIEF)

The IIEF is a validated 15-item for measuring patient-reported erectile function. A score of 0-5 is given to each of the 15 questions that examine 5 main domains of male sexual function: erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. Domain scores are the sum of each item. The erectile function domain has 5 items with a score range of 1-30, orgasmic function has 2 items with a score range of 0-10, sexual desire has 2 items with a score range of 0-10, intercourse satisfaction has 3 items with a score range of 0-15, and overall satisfaction has 2 items with a score range of 2-10. Total score ranges from 0-70, with higher scores indicated better functioning. Change from baseline is calculated by subtracting baseline score from score at the time point of interest.

Overall Patient Sexual Satisfaction as Measured by Change From Baseline in the Sexual Adjustment Questionnaire (SAQ) Score

The Sexual Adjustment Questionnaire (SAQ) is a 20-item questionnaire with an overall score range between 8 and 100 including the following domains: desire, ranging between 5 and 30; dysfunction, 0 and 25; activity, 0 and 10; satisfaction, 1 and 10; and fatigue, 1 and 5. The change in SAQ score is calculated by subtracting the baseline score from the follow-up score. A positive change indicates an improvement in sexual well-being.

Overall Partner Sexual Satisfaction as Measured by Change From Baseline in the Sexual Adjustment Questionnaire-Partner (SAQ-P) Score

The SAQ-P is an 18-item questionnaire with an overall score range between 0 and 90 including the following domains: desire, dysfunction, activity, satisfaction, and fatigue. The change in SAQ score is calculated by subtracting the baseline score from the follow-up score. A positive change indicates an improvement in sexual well-being.

Patient Marital Adjustment as Measured by the Locke's Marital Adjustment Test

The Locke Marital Adjustment Test (LMAT) is a 16-item questionnaire with scores ranging from 48 to 138 for participants. Higher scores indicate greater sexual function, sexual wellbeing, or marital adjustment. The change in LMAT score is calculated by subtracting the baseline score from the follow-up score.

Partner Marital Adjustment as Measured by the Locke's Marital Adjustment Test

Full Information

NCT ID

NCT00931528

First Posted

June 30, 2009

Last Updated

January 18, 2018

Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), NRG Oncology

1. Study Identification

Unique Protocol Identification Number

NCT00931528

Brief Title

Tadalafil in Preventing Erectile Dysfunction in Patients With Prostate Cancer Treated With Radiation Therapy

Official Title

A Randomized, Double-blind, Placebo-controlled Phase III Trial to Evaluate the Effectiveness of a Phosphodiesterase 5 Inhibitor, Tadalafil, in Prevention of Erectile Dysfunction in Patients Treated With Radiotherapy for Prostate Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radiation Therapy Oncology Group

Collaborators

National Cancer Institute (NCI), NRG Oncology

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Tadalafil may help prevent erectile dysfunction (ED) in patients with prostate cancer that has been treated with radiation therapy. It is not yet known whether tadalafil is more effective than a placebo in preventing erectile dysfunction. PURPOSE: This randomized phase III trial is studying tadalafil to see how well it works compared with a placebo in preventing erectile dysfunction in patients with prostate cancer treated with radiation therapy.

Detailed Description

OBJECTIVES: Primary To determine whether tadalafil maintains spontaneous (off-drug) erectile function, as measured by the International Index of Erectile Function (IIEF) as compared to placebo at weeks 28-30 after initiation of radiotherapy in patients with prostate cancer. Secondary Determine the difference in spontaneous (off-drug) erectile function between tadalafil and placebo at 1 and 2 years. Determine the difference in overall sexual function as measured by the IIEF between tadalafil and placebo at weeks 28-30 and at 1 and 2 years. Determine differences in patient and partner overall sexual satisfaction as measured by the Sexual Adjustment Questionnaire (SAQ) between tadalafil and placebo at weeks 28-30 and at 1 and 2 years. Determine differences in patient and partner marital adjustment as measured by Locke's Marital Adjustment Test (LMAT) between tadalafil and placebo at weeks 28-30 and at 1 and 2 years. Determine associations between patient and partner overall sexual satisfaction as measured by SAQ and patient and partner marital adjustment as measured by LMAT at weeks 28-30 and at 1 and 2 years. Determine patient-related factors (i.e., age, pretreatment sexual response, tobacco use, and comorbidities) that may predict response to tadalafil therapy at weeks 28-30 and at 1 and 2 years. Determine the difference in adverse events between tadalafil and placebo as assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 criteria. Tertiary Characterization of preference and erectile function among patients who choose to stay on (or if on placebo, to start) tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor other than tadalafil, a non-PDE5-inhibitor erectile aide, or no PDE5 inhibitor or erectile aide at 28-30 weeks and at 1 and 2 years. Identification of radiotherapy factors (i.e., modality, prescribed total dose, planning target volume margin, penile bulb dose-volume parameters) associated with erectile function. Evaluation of the number of patients screened for eligibility, the number eligible that are presented the study, the number who refuse, and the number who are accrued. OUTLINE: This is a multicenter study. Patients are stratified according to age (≤ 65 years vs > 65 years) and radiotherapy treatment (external beam radiation therapy vs brachytherapy*). Patients are randomized to 1 of 2 treatment arms. Note: * Radiotherapy start date for brachytherapy patients is the date of the procedure. All patients undergo either external beam radiotherapy alone to the prostate ± seminal vesicles only or low-dose rate permanent brachytherapy alone. Arm I: Beginning ≤ 7 days after the start of radiotherapy, patients receive oral tadalafil once daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Beginning ≤ 7 days after the start of radiotherapy, patients receive oral placebo once daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients complete the International Index of Erectile Function (IIEF), the Sexual Adjustment Questionnaire (SAQ), the Locke's Marital Adjustment Test (LMAT) (if applicable), and the Expanded Prostate Cancer Index Composite Sexual Medications and Devices Evaluations Supplement questionnaires periodically. Partners or spouses complete the SAQ-Partner, LMAT (if applicable), and IIEF questionnaires periodically. After completion of study treatment, patients are followed at 28-30 weeks, and annually for up to 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer, Sexual Dysfunction

Keywords

sexual dysfunction, stage IIB prostate cancer, stage IIA prostate cancer, adenocarcinoma of the prostate

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

242 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tadalafil

Arm Type

Experimental

Arm Description

Tadalafil

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Tadalafil

Intervention Description

Beginning ≤ 7 days after the start of radiotherapy, patients receive oral tadalafil 5mg once daily for 24 weeks.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Beginning ≤ 7 days after the start of radiotherapy, patients receive oral placebo once daily for 24 weeks.

Primary Outcome Measure Information:

Title

Percentage of Patients Maintaining Spontaneous (Off-drug) Erectile Function (EF) at Weeks 28-30 After Initiation of Radiation Therapy (RT)

Description

Time Frame

Baseline and 30 weeks from the start of radiation therapy

Secondary Outcome Measure Information:

Title

Percentage of Patients Maintaining Spontaneous (Off-drug) EF at Years 1 and 2 After Initiation of RT

Description

Time Frame

Baseline, 1 and 2 years from the start of tadalafil or placebo

Title

Overall Sexual Function as Measured by Change From Baseline in the International Index of Erectile Function (IIEF)

Description

Time Frame

Baseline, week 30, and years 1 and 2 from start of treatment

Title

Overall Patient Sexual Satisfaction as Measured by Change From Baseline in the Sexual Adjustment Questionnaire (SAQ) Score

Description

Time Frame