Luteinizing Hormone-Releasing Hormone Agonist Therapy and Iodine I 125 Implant in Treating Patients With Previously Untreated Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Androgens can cause the growth of prostate cancer cells. Luteinizing hormone-releasing hormone agonists may lessen the amount of androgens made by the body. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving luteinizing hormone-releasing hormone agonist together with an iodine I 125 implant may be an effective treatment for patients with prostate cancer. PURPOSE: This randomized phase III trial is studying how well giving luteinizing hormone-releasing hormone agonist therapy together with an iodine I 125 implant works with or without additional luteinizing hormone-releasing hormone agonist therapy in treating patients with previously untreated prostate cancer.

Detailed Description
-----------------
OBJECTIVES: To evaluate the biochemical progression-free survival (PFS), overall survival, clinical PFS, and disease-free survival of patients with previously untreated intermediate-risk prostate cancer treated with neoadjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy and permanent iodine I 125 implantation with vs without adjuvant LHRH agonist therapy. To determine the non-adaptive interval to salvage therapy in patients treated with these regimens. To determine the safety of these regimens in these patients. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive neoadjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy for up to 3 months and undergo permanent iodine I 125 implantation. Patients then receive adjuvant LHRH agonist therapy for up to 9 months. Arm II: Patients receive neoadjuvant LHRH agonist therapy and undergo permanent iodine I 125 implantation as in arm I.

Official Title
-----------------
A Phase III, Multicenter, Randomized, Controlled Study of Neoadjuvant LHRH-agonist Therapy and Permanent I-125 Implantation With vs. Without Adjuvant LHRH-agonist Therapy in Patients With Untreated Intermediate-risk Prostate Cancer.

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Adjuvant therapy
* Drug: Neoadjuvant therapy
* Radiation: Brachytherapy（iodine I 125）


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed prostate cancer Previously untreated disease Intermediate-risk disease, as defined by the following: Clinical stage < T2c Prostate-specific antigen (PSA) ≤ 20 ng/mL Gleason score < 8 PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 3 months Leukocyte count ≥ 3,000/uL Hemoglobin ≥ 10.0 g/dL Platelet count ≥ 100,000/uL Serum creatinine ≤ 2.0 mg/dL ALT and AST ≤ 100 IU/L No other cancer requiring treatment No poorly controlled hypertension (i.e., diastolic blood pressure ≥ 120 mm Hg) No severe psychiatric disorders, including schizophrenia or dementia No poorly controlled diabetes Considered appropriate for study participation, as determined by the Principal Investigator or Clinical Investigator PRIOR CONCURRENT THERAPY: No prior drugs for benign prostatic hyperplasia (other than antiandrogen therapy) No prior surgery for prostate cancer No concurrent steroid drugs (except for ointment) No other concurrent antiandrogen therapy

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AHT group<br>Randomized patients undergo 3-month neoadjuvant therapy (NHT)within 14 days and receive 9-month adjuvant therapy (AHT) following after Iodine I-125 implantation (TPPB). | Drug: Adjuvant therapy<br>* AHT group receives 9 cycle of LHRH-A (goserelin acetate 3.6 mg/4 weeks or leuprorelin acetate 3.75 mg/4 weeks) after Iodine I-125 implantation (TPPB).<br>Drug: Neoadjuvant therapy<br>* 3 cycle of LHRH-A (goserelin acetate 3.6mg/4 weeks or leuprorelin acetate 3.75mg/4 weeks).<br>Radiation: Brachytherapy（iodine I 125）<br>* Undergo Iodine I-125 transperineal prostatic brachytherapy (TPPB).<br>|
| Active Comparator: Non-AHT group<br>Rondomized patients undergo 3-month neoadjuvant therapy (NHT) within 14 days and receive Iodine I-125 implantation therapy (TPPB). 40 weeks observation is followed under no further treatment. | Drug: Neoadjuvant therapy<br>* 3 cycle of LHRH-A (goserelin acetate 3.6mg/4 weeks or leuprorelin acetate 3.75mg/4 weeks).<br>Radiation: Brachytherapy（iodine I 125）<br>* Undergo Iodine I-125 transperineal prostatic brachytherapy (TPPB).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical progression-free survival (bPFS) | Interval from the 1st day of treatement to the earliest day on which confirmation of increase in prostate specific antigen (PSA) or death any reason. | 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Interval from the 1st day of treatment to the earliest day of death any reason. | 13.5 years | 
| Clinical progression-free survival | Interval from the 1st day of treatment to the ealiest day on which identification of desease progression or death for any reason. | 7 years | 
| Disease-specific survival | Interval from the 1st day of treatment to death caused by prostate cancer | 7 years | 
| Salvage therapy non-adaptive interval | Observational term as salvage therapy non-adaptive interval. | 7 years | 
| Quality of life (QOL) evaluation | QOL assesed by the Japanese version of the SF-8 (the MOS 8 item Short-Form Health Survey), the Japanese version of the Expanded Prostate Cancer Index Composite (EPIC), and the International Prostate Sympton Score (IPSS). | Baseline and Month 60 after TPPB | 
| Adverse events (AE) | The incident propotion of adverse event grade above 3 by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0) will be compared. | AE to androgen-deprivation therapy (ADT) within 24 month, AE to 125I-transperineal prostatic brachytherapy (TPPB) within 36 month of the therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IIB prostate cancer, stage IIA prostate cancer, stage I prostate cancer