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

November 3, 2009
July 29, 2015
April 2004
December 2007   (final data collection date for primary outcome measure)
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.
HOT FLUSHES score in week 4 of treatment after randomisation (variation in average score compared with evaluation at randomisation visit V1, expressed as a percentage). [ Time Frame: in week 4 of treatment after randomisation ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01011751 on ClinicalTrials.gov Archive Site
  • 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.
  • Frequency of HF week 4 [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
  • % of patients with more than 50% decrease in HF [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
  • % of patients having a decrease in the level of complaint HF [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
  • HF frequency between week 4 and 8 [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
  • % of patients who wish to continue after week 10 [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
  • Quality of life(QLQ C30) [ Time Frame: 4 and 8 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Treatment of Hot Flushes Caused by Leuprorelin 11.25 mg in Prostate Adenocarcinoma
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Adenocarcinoma, Prostate
  • Drug: Cyproterone acetate
    Cyproterone acetate tablet-in-capsule.
    Other Name: Androcur® 50 mg
  • Drug: Medroxyprogesterone acetate
    Medroxyprogesterone acetate tablet-in-capsule.
    Other Name: Gestoral® 10 mg
  • 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.
  • 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.
    Interventions:
    • Drug: Cyproterone acetate
    • Drug: Leuprorelin
    • Drug: Flutamide
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Medroxyprogesterone acetate
    • Drug: Leuprorelin
    • Drug: Flutamide
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Venlafaxine
    • Drug: Leuprorelin
    • Drug: Flutamide
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
311
December 2007
December 2007   (final data collection date for primary outcome measure)

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.
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01011751
F-LEU-100, U1111-1169-6822
No
Takeda
Takeda
Not Provided
Principal Investigator: jacques irani, MD Poitiers hospital
Takeda
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP