Treatment of Hot Flushes Caused by Leuprorelin 11.25 mg in Prostate Adenocarcinoma

NCT01011751 | Completed Phase 3

• 2 other identifiers: F-LEU-100U1111-1169-6822
• Study Type: interventional
• Target: 311
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenocarcinoma, Prostate

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Percent Change from Randomization in Hot Flushes (HF) Score at Week 4 of Treatment

  The change is calculated as follows: \[(HF score at Week 4 of treatment - HF score at randomization)/HF score at randomization\]\*100. The calculation of the HF score will be done as follows: a coefficient is allocated to each severity grade, it varies from 1 to 4 (1: slight; 2: moderate; 3: severe; 4: very severe), and the calculation of the daily score is equal to the sum of the daily instances of hot flushes multiplied by their severity coefficient. The score calculated at randomization and Week 4 of treatment will be the average of the scores recorded in the preceding week. The score range will depend upon the frequency of hot flushes, and higher score signifies higher severity of hot flushes.

  Randomization (Month 6) and Week 4 of treatment (Month 7)

Secondary Outcomes (11)

• Percent Change from Randomization in HF Frequency at Weeks 4, 8 of Treatment and Last Available Value

  Randomization (Month 6), Weeks 4 and 8 of treatment (Months 7 and 8, respectively) and last available value (Month 7 or 8)

• Percentage of Participants With More Than 50 percent (%) Decrease in HF Score

  Week 4 of treatment

• Percentage of Participants with Complete Regression of hot flushes

  Week 4 of treatment

• Percentage of Participants With A Decrease in the Level of HF Complaint

  Weeks 4 and 8 of treatment and Week 12 after the start of treatment

• Percent Change in HF Score from Randomization at Week 8 of Treatment and Last Available Value

  Randomization, Week 8 of treatment, and last available value (Month 7 or 8)

Study Arms (3)

Cyproterone acetate

EXPERIMENTAL

Leuprorelin 11.25 mg, injection, subcutaneously at Months 0, 3, and 6, and flutamide 250 mg, tablet, orally, thrice daily for first 30 days from first leuprorelin administration. From Month 6, cyproterone acetate 50 mg, tablet-in-capsule, along with cyproterone acetate placebo-matching capsule, orally, once daily in the morning and cyproterone acetate 50 mg, tablet-in-capsule, orally, once daily in the evening for 8 weeks. Cyproterone acetate placebo-matching capsule, orally, once daily in the morning for the next 2 weeks.

Drug: Cyproterone acetate; Drug: Leuprorelin; Drug: Flutamide; Drug: Placebo

Medroxyprogesterone acetate

EXPERIMENTAL

Leuprorelin 11.25 mg, injection, subcutaneously at Months 0, 3, and 6, and flutamide 250 mg, tablet, orally, thrice daily for first 30 days from first leuprorelin administration. From Month 6, medroxyprogesterone acetate 10 mg, tablet-in-capsule, along with medroxyprogesterone acetate placebo-matching capsule, orally, once daily in the morning and medroxyprogesterone acetate 10 mg, tablet-in-capsule, orally, once daily in the evening for 8 weeks. Medroxyprogesterone acetate placebo-matching capsule, orally, once daily in the morning for the next 2 weeks.

Drug: Medroxyprogesterone acetate; Drug: Leuprorelin; Drug: Flutamide; Drug: Placebo

Venlafaxine

EXPERIMENTAL

Leuprorelin 11.25 mg, injection, subcutaneously at Months 0, 3, and 6, and flutamide 250 mg, tablet, orally, thrice daily for first 30 days from first leuprorelin administration. From Month 6, venlafaxine 75 mg, capsule, orally, once daily in the morning and venlafaxine placebo-matching capsule, orally, once daily in the evening for 8 weeks. Venlafaxine 37.5 mg, capsule, orally, once daily in the evening for the next 2 weeks.

Drug: Venlafaxine; Drug: Leuprorelin; Drug: Flutamide; Drug: Placebo

Interventions

Cyproterone acetate DRUG

Cyproterone acetate tablet-in-capsule.

Also known as: Androcur® 50 mg

Cyproterone acetate

Medroxyprogesterone acetate DRUG

Medroxyprogesterone acetate tablet-in-capsule.

Also known as: Gestoral® 10 mg

Medroxyprogesterone acetate

Venlafaxine DRUG

Venlafaxine capsule.

Also known as: Effexor® LP 37.5 mg

Venlafaxine

Leuprorelin DRUG

Leuprorelin injection.

Also known as: Enantone® 11.25 mg

Cyproterone acetate; Medroxyprogesterone acetate; Venlafaxine

Flutamide DRUG

Flutamide tablet

Cyproterone acetate; Medroxyprogesterone acetate; Venlafaxine

Placebo DRUG

Cyproterone acetate, medroxyprogesterone acetate or venlafaxine placebo-matching capsule.

Cyproterone acetate; Medroxyprogesterone acetate; Venlafaxine

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Professor Jacques IRANI

Poitiers, Poitiers, 86021, France

Location

Related Publications (1)

• 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.

  PMID: 19963436 DERIVED

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Cyproterone Acetate; Medroxyprogesterone Acetate; Venlafaxine Hydrochloride; Leuprolide; Flutamide

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cyproterone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Anilides; Amides; Aniline Compounds

Study Officials

• jacques irani, MD

  Poitiers hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2009
• First Posted: November 11, 2009
• Study Start: April 1, 2004
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: July 30, 2015

Record last verified: 2015-07

Locations

FR (1)