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

Takeda

Status and phase: Completed; Phase 3

Conditions: Adenocarcinoma, Prostate

Treatments: Drug: Leuprorelin; Drug: Medroxyprogesterone acetate; Drug: Cyproterone acetate; Drug: Venlafaxine; Drug: Placebo; Drug: Flutamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01011751

F-LEU-100

U1111-1169-6822 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 311 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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311 participants in 3 patient groups

Cyproterone acetate

Experimental group

Description:

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.

Treatment:

Drug: Flutamide

Drug: Placebo

Drug: Cyproterone acetate

Drug: Leuprorelin

Medroxyprogesterone acetate

Experimental group

Description:

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.

Treatment:

Drug: Flutamide

Drug: Placebo

Drug: Medroxyprogesterone acetate

Drug: Leuprorelin

Venlafaxine

Experimental group

Description:

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.

Treatment:

Drug: Flutamide

Drug: Placebo

Drug: Venlafaxine

Drug: Leuprorelin