Leuprorelin Associated With Radiotherapy Versus Leuprorelin Alone in T3 - T4 or pT3 (on Biopsy) N0, M0 Prostate Cancer

Takeda

Status and phase: Completed; Phase 3

Conditions: Prostatic Neoplasms, Locally Advanced

Treatments: Radiation: Radiotherapy; Drug: Leuprorelin SR; Drug: Flutamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01122121

U1111-1169-6728 (Registry Identifier)

TAP III/98/032

Details and patient eligibility

About

The purpose of this study is to compare the efficacy and safety of combined radiotherapy and hormone therapy and hormone therapy alone in the treatment of clinically locally advanced prostate cancer (T3-T4 or pT3 on biopsy, N0, M0).

Full description

The drug being tested in this study is called leuprorelin SR. Leuprorelin SR is being tested to treat people who have prostate cancer. This study will look at the overall survival of people who take leuprorelin SR in addition to radiation therapy compared to those who take only leuprorelin SR.

The study will enroll approximately 273 patients. Participants will be randomly assigned to one of the two treatment groups.

• Combined Radiotherapy and Hormone Therapy
• Hormone Therapy alone. All participants will receive leuprorelin injection every 3 months and flutamide tablets thrice daily for first 30 days as part of hormone therapy. Participants randomized to combined radiotherapy and hormone therapy group, will also receive radiotherapy 70 +/- 4 Gy in 35 fractions at a rate of 5 fractions of 2 Gy per week.

This multi-center trial will be conducted in France and Tunisia. The overall time to participate in this study is 8 years. The scheduled duration of hormone therapy was 3 years in both arms, with an additional treatment-free follow-up period of 2 years i.e. a total follow-up period of 5 years. Post-protocol collection of information relative to survival will be performed after the end the 5-year follow-up period.

Enrollment: 273 patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed locally advanced adenocarcinoma of the prostate, graded: T3 or T4 or pT3 on biopsies (presence of tumour tissue in periprostatic fat observed on biopsies), N0 (absence of metastatic), M0 (no distant metastases detectable on the following examinations: bone scan, chest x-ray, abdominal and pelvic ultrasound).
• Patient in whom the prostatic adenocarcinoma has received no prior treatment of any type, with the possible exception of transurethral resection due to obstructive symptoms.
• Patient with a Karnofsky index greater than or equal to (≥) 70.
• Patient aged under 80 years on the randomization date.
• Patient with a life expectancy of at least 7 years.
• Patient who, after having received clear information, gave his written consent to participate and cooperate in the study.
• Patient for whom a recent blood test (less than [<] 2 months) has not revealed elevated transaminases ≥ 3 times the normal laboratory range.

Exclusion criteria

• Patient incapable of understanding the information supplied concerning the study or of giving his consent, or having refused to sign the informed consent form,
• Patient for whom there is a risk that follow-up in compliance with the conditions stipulated by the protocol will not be possible,
• Patient having already received prior treatment for prostate cancer, excluding transurethral resection of the prostate to relieve obstruction,
• Patient having undergone surgical castration, or with a history of bilateral adrenalectomy or hypophysectomy,
• Patient having had another cancer within the previous 5 years (including carcinoma in situ of the bladder) excluding basocellular epithelioma or carcinoma in situ (other than in the bladder),
• Patient with lymph node or metastatic spread of the prostatic adenocarcinoma suspected on imaging,
• Patient with a non-controlled severe active disease,
• Patient with a contraindication to external prostatic radiotherapy,
• Patient receiving or having received another experimental treatment within 3 months prior to inclusion in the study,
• Patient with impaired liver function or elevated transaminases ≥3 times the normal laboratory range.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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273 participants in 2 patient groups

Combined Radiotherapy and Hormone Therapy

Experimental group

Description:

Leuprorelin 11.25 milligram (mg) sustained release (SR), injection, subcutaneously, once every 3 months up to 3 years and flutamide 250 mg, tablet, orally, thrice daily for 30 days from the first dose of leuprorelin. Radiotherapy 70 +/- 4 Gray (Gy) in 35 fractions at a rate of 5 fractions of 2 Gy per week up to 3 years. An interval of a maximum of 2 weeks is authorized between radiation of the pelvis with 50 Gy (±4) (5 weeks) and radiation of the prostate with an additional 20 Gy.

Treatment:

Radiation: Radiotherapy

Drug: Leuprorelin SR

Drug: Flutamide

Hormone Therapy alone

Active Comparator group

Description:

Leuprorelin 11.25 mg SR, injection, subcutaneously, once every 3 months up to 3 years and flutamide 250 mg, tablet, orally, thrice daily for 30 days from the first dose of leuprorelin.

Treatment:

Drug: Leuprorelin SR

Drug: Flutamide