Luteinizing Hormone-Releasing Hormone Agonist Therapy and Iodine I 125 Implant in Treating Patients With Previously Untreated Prostate Cancer (SHIP0804)

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.

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Adjuvant therapy; Drug: Neoadjuvant therapy; Radiation: Brachytherapy（iodine I 125）

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.

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 125-8506
    • The Jikei University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AHT group; 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; 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).; Drug: Neoadjuvant therapy; 3 cycle of LHRH-A (goserelin acetate 3.6mg/4 weeks or leuprorelin acetate 3.75mg/4 weeks).; Radiation: Brachytherapy（iodine I 125）; Undergo Iodine I-125 transperineal prostatic brachytherapy (TPPB).
Active Comparator: Non-AHT group; 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; 3 cycle of LHRH-A (goserelin acetate 3.6mg/4 weeks or leuprorelin acetate 3.75mg/4 weeks).; Radiation: Brachytherapy（iodine I 125）; Undergo Iodine I-125 transperineal prostatic brachytherapy (TPPB).

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

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Collaborators: The Jikei University School of Medicine
• Investigators: Principal Investigator: Shin Egawa, MD, PhD, The Jikei University School of Medicine

Publications and helpful links

General Publications

• Miki K, Kiba T, Sasaki H, Kido M, Aoki M, Takahashi H, Miyakoda K, Dokiya T, Yamanaka H, Fukushima M, Egawa S. Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial. BMC Cancer. 2010 Oct 21;10:572. doi: 10.1186/1471-2407-10-572.
• Tabata R, Kimura T, Kuruma H, Sasaki H, Kido M, Miki K, Takahashi H, Aoki M, Egawa S. Do androgen deprivation and the biologically equivalent dose matter in low-dose-rate brachytherapy for intermediate-risk prostate cancer? Cancer Med. 2016 Sep;5(9):2314-22. doi: 10.1002/cam4.820. Epub 2016 Jul 25.
• Sasaki H, Kido M, Miki K, Aoki M, Takahashi H, Dokiya T, Yamanaka H, Fukushima M, Egawa S. Results of central pathology review of prostatic biopsies in a contemporary series from a phase III, multicenter, randomized controlled trial (SHIP0804). Pathol Int. 2015 Apr;65(4):177-82. doi: 10.1111/pin.12260. Epub 2015 Feb 24.
• Sasaki H, Kido M, Miki K, Kuruma H, Takahashi H, Aoki M, Egawa S. Salvage partial brachytherapy for prostate cancer recurrence after primary brachytherapy. Int J Urol. 2014 Jun;21(6):572-7. doi: 10.1111/iju.12373. Epub 2013 Dec 23.
• Kimura T, Kido M, Miki K, Yamamoto T, Sasaki H, Kuruma H, Hayashi N, Takahashi H, Aoki M, Egawa S. Mid-term outcome of permanent prostate iodine-125 brachytherapy in Japanese patients. Int J Urol. 2014 May;21(5):473-8. doi: 10.1111/iju.12347. Epub 2013 Nov 20.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2008
• Primary Completion (Actual): April 24, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: April 22, 2008
• First Submitted That Met QC Criteria: April 22, 2008
• First Posted (Estimated): April 23, 2008

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: BRIGU05-01; CDR0000593653 (Other Identifier: National Cancer Institute)