Tadalafil in Preventing Erectile Dysfunction in Patients With Prostate Cancer Treated With Radiation Therapy
Condition: Prostate Cancer; Sexual Dysfunction
MeSH terms: Prostatic Neoplasms; Erectile Dysfunction
Intervention: Tadalafil; Placebo
Intervention description: Beginning ≤ 7 days after the start of radiotherapy, patients receive oral tadalafil 5mg once daily for 24 weeks.; Beginning ≤ 7 days after the start of radiotherapy, patients receive oral placebo once daily for 24 weeks.
Intervention MeSH terms: Tadalafil
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 242.0
Sex: Male
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: sexual dysfunction; stage IIB prostate cancer; stage IIA prostate cancer; adenocarcinoma of the prostate

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Clinical stage T1b-T2b (AJCC, 6th ed.) adenocarcinoma of the prostate within 6 months
             of registration

          2. 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.

          3. 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.

          4. 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

          5. Serum total testosterone level prior to the initiation of radiation therapy (RT)
             within normal range according to institutional guidelines

          6. Zubrod Performance Status 0 or 1 (Appendix III)

          7. Age ≥ 18 years

          8. 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)

          9. 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]

         10. 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.

         11. 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:

          1. The patient's participation in another medical research study that involves the
             treatment of ED

          2. 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

          3. History of myocardial infarction within the last year

          4. Heart failure in the last 6 months

          5. Uncontrolled arrhythmias, hypotension (<90/50mm Hg), or uncontrolled hypertension
             (>170/100 mm Hg)

          6. Stroke within the last 6 months

          7. 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

          8. Current use of any organic nitrate or as needed nitrates (e.g., use of nitroglycerin)

          9. Current use of cimetidine, ketoconazole, itraconazole, erythromycin, or ritonavir

         10. Known moderate to severe renal insufficiency or end-stage renal disease

         11. Known severe hepatic impairment

         12. 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

         13. 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]

         14. Prior penile implant or history of bilateral orchiectomy

         15. Prior prostatectomy, prostatic cryosurgery or high-intensity focused ultrasound
             (HIFU), radionuclide prostate brachytherapy, or chemotherapy for prostate cancer

         16. Prior or anticipated combined external RT and brachytherapy

         17. Prior or anticipated external RT to the pelvic ± para-aortic lymph nodes

         18. 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.

         19. Anatomical genital abnormalities or concurrent conditions that in the estimation of
             the physician would prohibit sexual intercourse or prevent study completion

         20. Major medical or psychiatric illness which, in the opinion of the investigator, would
             prevent completion of treatment or would interfere with follow-up