Clinical trial NCT01011751: Treatment of Hot Flushes Caused by Leuprorelin 11.25 mg in Prostate Adenocarcinoma
Official title: Efficacy and Tolerance of Cyproterone Acetate Versus Medroxyprogesterone Acetate Versus Venlafaxine LP in the Treatment of Hot Flushes Caused by Leuprorelin 11.25 mg in Patients Treated for a Prostate Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adenocarcinoma, Prostate
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 311
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy of three drugs (cyproterone acetate, medroxyprogesterone acetate and venlafaxine) in the treatment of hot flushes caused by leuprorelin LP 11.25 milligram (mg) in participants suffering from prostate cancer.

Detailed description: Three drugs will be tested in this study: cyproterone acetate, medroxyprogesterone acetate and venlafaxine. Cyproterone acetate, medroxyprogesterone acetate and venlafaxine are being tested to treat men who suffer from hot flushes due to androgen suppression treatment for prostate cancer. This study will look at the frequency and severity of hot flushes caused by leuprorelin in participants who will take cyproterone acetate, medroxyprogesterone acetate or venlafaxine. The study will randomize approximately 311 participants. All participants will receive 2 injections of leuprorelin 11.35 mg at Months 0 and 3 along with flutamide tablets in the first month of treatment to prevent flare-up. After 6 months, eligible participants will receive third injection of leuprorelin and will be randomly assigned to one of the three treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Cyproterone acetate (Androcur® 50 mg)
* Medroxyprogesterone acetate (Gestoral® 10 mg)
* Venlafaxine (Effexor® LP 37.5 mg) All participants will be asked to take 2 capsules in the morning and 1 capsule in the evening for 10 weeks. All participants will be asked to complete the self-evaluation hot-flushes (HF) questionnaire daily for 12 weeks from the start of treatment for hot flushes.

This multi-center trial will be conducted in France. The overall time to participate in this study is approximately 9 months. Participants will make 5 visits to the clinic during the study.

Eligibility criteria: Inclusion Criteria: - Patient has a histologically proven prostatic adenocarcinoma.

* Patient has been on a gonadotropin releasing hormone (GnRH) agonist treatment for a duration of at least 1 year.
* Karnofsky index greater than or equal to (\>=) 70 %.
* Patient who, after having been clearly informed, has given his written consent to participate in the study.

Exclusion Criteria:

* Patient included in a therapeutic trial in the 3 months preceding the inclusion visit.
* Prescription of agonist planned in the context of neo-adjuvant hormonotherapy.
* Patient has symptomatic bone metastases.
* Patient already treated with hormonotherapy for his prostate cancer or has received a hormonal treatment other than a GnRH agonist for this cancer (apart from palliative care of flare-up with anti-androgens).
* Patient is unable to understand the information regarding the study provided to him, of giving his consent or who has refused to sign the informed consent sheet.
* Patient for whom risk follow up could not be guaranteed within the conditions stipulated in the protocol or is unable to complete the self-evaluation questionnaires.
* Diabetic, or patient with severe progressive disease: kidney, liver, cardiovascular (especially high uncontrolled BP), psychiatric.
* Has a Thromboembolic history or concomitant thromboembolic disease.
* Patient had hepatocellular insufficiency or hepatic cytolysis (serum glutamic oxaloacetic transaminase / serum glutamic pyruvate transaminase \[SGOT/SGPT\] \>3 times laboratory normal range).
* Patient had a contra-indication to one of the study drugs.
* Patient receiving corticotherapy or concomitant prescription for non-selective monoamine oxidase inhibitors (MAOI), serotonin re-uptake inhibitors, clonidine, gabapentine, veripride, tibolone or beta-alanine.
* Patient was undergoing medical treatment for a depressive phase or had been treated for this during the previous 2 years before inclusion.
* Patient with a history of congenital galactosemy, poor absorption of glucose or galactose syndrome or even a lactase deficiency.
* Patient had another cancer in the 5 previous years excluding basocellular epithelioma or in situ carcinoma.

Primary outcomes:
measure: Percent Change from Randomization in Hot Flushes (HF) Score at Week 4 of Treatment
timeFrame: Randomization (Month 6) and Week 4 of treatment (Month 7)
Secondary outcomes:
measure: Percent Change from Randomization in HF Frequency at Weeks 4, 8 of Treatment and Last Available Value
timeFrame: Randomization (Month 6), Weeks 4 and 8 of treatment (Months 7 and 8, respectively) and last available value (Month 7 or 8)
measure: Percentage of Participants With More Than 50 percent (%) Decrease in HF Score
timeFrame: Week 4 of treatment
measure: Percentage of Participants with Complete Regression of hot flushes
timeFrame: Week 4 of treatment
measure: Percentage of Participants With A Decrease in the Level of HF Complaint
timeFrame: Weeks 4 and 8 of treatment and Week 12 after the start of treatment
measure: Percent Change in HF Score from Randomization at Week 8 of Treatment and Last Available Value
timeFrame: Randomization, Week 8 of treatment, and last available value (Month 7 or 8)
measure: Percent Change from Week 4 of treatment in HF Score at Week 8 of Treatment
timeFrame: Weeks 4 and 8 of treatment
measure: Percent Change from Week 4 of treatment in HF Frequency at Week 8 of Treatment
timeFrame: Weeks 4 and 8 of treatment
measure: Percentage of Participants Who Wish to Continue the Treatment at the End of Week 10
timeFrame: Weeks 8 and 12 after the start of treatment
measure: Percentage of Participants Who Wish to Restart the Treatment at the End of Week 12
timeFrame: Week 12 after the start of treatment
measure: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline (Month 0), randomization (Month 6), Weeks 4 and 8 of treatment, Week 12 after the start of treatment
measure: Participant's Satisfaction About Treatment
timeFrame: Week 4, 8 of treatment, and Week 12 after the start of treatment
Other outcomes:
Locations:
city: Poitiers
country: France
facility: Professor Jacques IRANI
Study officials:
affiliation: Poitiers hospital
name: jacques irani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Irani J, Salomon L, Oba R, Bouchard P, Mottet N. Efficacy of venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for the treatment of vasomotor hot flushes in men taking gonadotropin-releasing hormone analogues for prostate cancer: a double-blind, randomised trial. Lancet Oncol. 2010 Feb;11(2):147-54. doi: 10.1016/S1470-2045(09)70338-9. Epub 2009 Dec 4.