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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01011751
First received: November 3, 2009
Last updated: July 29, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma, Prostate
Drug: Cyproterone acetate
Drug: Medroxyprogesterone acetate
Drug: Venlafaxine
Drug: Leuprorelin
Drug: Flutamide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percent Change from Randomization in Hot Flushes (HF) Score at Week 4 of Treatment [ Time Frame: Randomization (Month 6) and Week 4 of treatment (Month 7) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percent Change from Randomization in HF Frequency at Weeks 4, 8 of Treatment and Last Available Value [ Time Frame: Randomization (Month 6), Weeks 4 and 8 of treatment (Months 7 and 8, respectively) and last available value (Month 7 or 8) ] [ Designated as safety issue: No ]
    The change is calculated as follows: [(HF frequency at specified Week of treatment - HF frequency at randomization)/HF score at randomization]*100.

  • Percentage of Participants With More Than 50 percent (%) Decrease in HF Score [ Time Frame: Week 4 of treatment ] [ Designated as safety issue: No ]
    The percentage of participants with at least 50 % improvement in HF score after 4 weeks of treatment compared to randomization will be calculated. 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 range will depend upon the frequency of hot flushes, and higher score signifies higher severity of hot flushes. The score calculated at randomization and Week 4 of treatment will be the average of the scores recorded in the preceding week.

  • Percentage of Participants with Complete Regression of hot flushes [ Time Frame: Week 4 of treatment ] [ Designated as safety issue: No ]
    Complete regression at Week 4 of treatment signifies complete disappearance of hot flushes upon 4 weeks of treatment.

  • Percentage of Participants With A Decrease in the Level of HF Complaint [ Time Frame: Weeks 4 and 8 of treatment and Week 12 after the start of treatment ] [ Designated as safety issue: No ]
    Decrease (improvement) in the level of complaint regarding hot flushes will be assessed compared to randomization. Participants' level of complaints about hot flushes was recorded at each visit of the study. The change in the level of complaints will be classified as degradation, non-change or improvement.

  • Percent Change in HF Score from Randomization at Week 8 of Treatment and Last Available Value [ Time Frame: Randomization, Week 8 of treatment, and last available value (Month 7 or 8) ] [ Designated as safety issue: No ]
    The change is calculated as follows: [(HF score at specified Week 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 range will depend upon the frequency of hot flushes, and higher score signifies higher severity of hot flushes. The score calculated at randomization and Week 8 of treatment will be the average of the scores recorded in the preceding week.

  • Percent Change from Week 4 of treatment in HF Score at Week 8 of Treatment [ Time Frame: Weeks 4 and 8 of treatment ] [ Designated as safety issue: No ]
    The change is calculated as follows: [(HF score at Week 8 of treatment - HF score at Week 4 of treatment)/HF score at Week 4 of treatment]*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 range will depend upon the frequency of hot flushes, and higher score signifies higher severity of hot flushes. The score calculated at Weeks 4 and 8 of treatment will be the average of the scores recorded in the preceding week.

  • Percent Change from Week 4 of treatment in HF Frequency at Week 8 of Treatment [ Time Frame: Weeks 4 and 8 of treatment ] [ Designated as safety issue: No ]
    The change is calculated as follows: [(HF frequency at Week 8 of treatment - HF frequency at Week 4 of treatment)/HF score at Week 4 of treatment]*100.

  • Percentage of Participants Who Wish to Continue the Treatment at the End of Week 10 [ Time Frame: Weeks 8 and 12 after the start of treatment ] [ Designated as safety issue: No ]
    Participants will be asked at Week 8 and 12 visits if they would like to continue the study treatment beyond the protocol-specified 10 weeks of treatment.

  • Percentage of Participants Who Wish to Restart the Treatment at the End of Week 12 [ Time Frame: Week 12 after the start of treatment ] [ Designated as safety issue: No ]
    Participants will be asked at Week 12 visit if they would like to restart the study treatment which ended after 10 weeks.

  • European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Baseline (Month 0), randomization (Month 6), Weeks 4 and 8 of treatment, Week 12 after the start of treatment ] [ Designated as safety issue: No ]
    EORTC QLQ-C30: includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions uses 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions uses 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; for the 5 functional scales and the global quality-of-life scale, a higher score represents a better level of functioning. For the symptom-oriented scales and items, a higher score corresponds to a higher level of symptoms.

  • Participant's Satisfaction About Treatment [ Time Frame: Week 4, 8 of treatment, and Week 12 after the start of treatment ] [ Designated as safety issue: No ]
    Participant's satisfaction is assessed by asking them how they would rate the treatment efficacy as not very effective, moderately effective and very effective at 4, 8 weeks of treatment and 12 weeks after the start of treatment.


Enrollment: 311
Study Start Date: April 2004
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cyproterone acetate
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
Cyproterone acetate tablet-in-capsule.
Other Name: Androcur® 50 mg
Drug: Leuprorelin
Leuprorelin injection.
Other Name: Enantone® 11.25 mg
Drug: Flutamide
Flutamide tablet
Drug: Placebo
Cyproterone acetate, medroxyprogesterone acetate or venlafaxine placebo-matching capsule.
Experimental: Medroxyprogesterone acetate
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
Medroxyprogesterone acetate tablet-in-capsule.
Other Name: Gestoral® 10 mg
Drug: Leuprorelin
Leuprorelin injection.
Other Name: Enantone® 11.25 mg
Drug: Flutamide
Flutamide tablet
Drug: Placebo
Cyproterone acetate, medroxyprogesterone acetate or venlafaxine placebo-matching capsule.
Experimental: Venlafaxine
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
Venlafaxine capsule.
Other Name: Effexor® LP 37.5 mg
Drug: Leuprorelin
Leuprorelin injection.
Other Name: Enantone® 11.25 mg
Drug: Flutamide
Flutamide tablet
Drug: Placebo
Cyproterone acetate, medroxyprogesterone acetate or venlafaxine placebo-matching capsule.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011751

Locations
France
Professor Jacques IRANI
Poitiers, France, 86021
Sponsors and Collaborators
Takeda
Investigators
Principal Investigator: jacques irani, MD Poitiers hospital
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01011751     History of Changes
Other Study ID Numbers: F-LEU-100, U1111-1169-6822
Study First Received: November 3, 2009
Last Updated: July 29, 2015
Health Authority: France: Institutional Ethical Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Takeda:
Drug Therapy

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Cyproterone
Cyproterone Acetate
Flutamide
Medroxyprogesterone
Medroxyprogesterone Acetate
Venlafaxine
Androgen Antagonists
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Central Nervous System Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 30, 2015