Hypo-fractionated Radiation Therapy With or Without Androgen Suppression for Intermediate Risk Prostate Cancer

Phase III Study of Image Guided Radiation Therapy With or Without Androgen Suppression for Intermediate Risk Adenocarcinoma of the Prostate

The purpose of this study is to compare the effects, good and/or bad of two treatment methods on subjects and their cancer.

Proton beam radiation therapy is one of the treatments for men with prostate cancer who have localized disease. The benefit of the combination with androgen suppression is not completely understood. This study will compare the use of hypofraction proton therapy (28 treatments) alone to proton therapy with androgen suppression therapy.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiation; Drug: Androgen Suppression Therapy

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Matthew Morocco; Phone Number: 630-836-8670; Email: mmorocco@pcgresearch.org

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Recruiting
      • Mayo Clinic
      • Contact: : Clinical Trials Office - All Mayo Clinic Locations; Phone Number: 855-776-0015 (toll free)
  • Illinois
    • Warrenville, Illinois, United States, 60555
      • Recruiting
      • Northwestern Medicine Chicago Proton Center
      • Contact: Don Smith, MS, CCRC; Phone Number: 630-933-7820; Email: donald.smith3@nm.org
      • Principal Investigator: Stephen Mihalcik, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73142
      • Recruiting
      • Oklahoma Proton Center
      • Contact: Jenny Washington, BSRT(T), CMD; Phone Number: 405-773-6700; Email: jenny.washington@okcproton.com
      • Principal Investigator: John Chang, MD
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Recruiting
      • Hampton University Proton Therapy Institute
      • Contact: Donna Sternberg, RN, BSN, OCN; Phone Number: 757-251-6839; Email: donna.sternberg@hamptonproton.org
      • Principal Investigator: Christopher Sinesi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed prostate adenocarcinoma (within 365 days of randomization) at intermediate risk for reoccurrence determined by at least one of the following: Gleason Score 7, PSA > = 10 and < = 20, T stage T2b - T2c
• Clinical stages T1-T2c N0 M0 as staged by the treating investigator. (AJCC Criteria 7th Ed.- appendix III).
• Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material; Gleason score must be in the range of 2-7. > 6 cores are strongly recommended.
• PSA values < = 20 ng/ml within 90 days prior to randomization. Obtained prior to biopsy or at least 21 days after prostate biopsy.
• ECOG performance status 0-1 (appendix II) assessed within 90 days of randomization.
• Patients must sign IRB approved study specific informed consent.
• Patients must complete all required pre-entry tests listed in section 4.0 within the specified time frames.
• Patients must be able to start treatment within 56 days of randomization.
• Patients must be at least 18 years old.
• For brachytherapy, an IPSS ≤ 21, or ≤ 17 if patient is on medications to improve urination.
• For brachytherapy, prostate volume must be less than 55cc prior to AS.

Exclusion Criteria:

• Pelvic lymph nodes > 1.5 cm in greatest dimension unless the enlarged lymph node is biopsied and negative.
• Previous prostate cancer surgery to include: prostatectomy, hyperthermia and cryosurgery.
• Previous pelvic radiation for prostate cancer.
• Previous androgen suppression therapy for prostate cancer.
• Active rectal diverticulitis, Crohn's disease affecting the rectum or ulcerative colitis (non-active diverticulitis and Crohn's disease not affecting the rectum are allowed).
• Prior systemic chemotherapy for prostate cancer.
• History of proximal urethral stricture requiring dilatation.
• Current and continuing anticoagulation with warfarin sodium (Coumadin), heparin, low- molecular weight heparin, Clopidogrel bisulfate (Plavix), or equivalent (unless it can be stopped to manage treatment related toxicity or to have a biopsy if needed).
• Major medical, addictive or psychiatric illness which in the investigator's opinion, will prevent the consent process, completion of the treatment and/or interfere with follow-up. (Consent by legal authorized representative is not permitted for this study).
• Evidence of any other cancer within the past 5 years and < 50% probability of a 5 year survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell cancer of the skin is allowed).
• History of myocardial infarction within the last 6 months.

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: Radiation Alone; Proton Radiation Total Dose=70 Gy(RBE) OR High Dose Radiation with IMRT Alone=81 Gy OR Intraoperative LDR Brachytherapy and IMRT=45 Gy	Radiation: Radiation; Consists of: Conformal Proton Radiation Dose: 2.5 Gy (RBE) five days a week in 28 treatments over 5.5-6.5 weeks (total dose: 70 Gy (RBE)); High Dose Radiation with IMRT alone: 1.8 Gy five days a week in 45 treatments over 9-10 weeks (total dose: 81 Gy); Intraoperative LDR Brachytherapy and IMRT: 100Gy Pad103 implant and IMRT 1.8 Gy five days a week in 25 treatments over 5-6 weeks (total dose: 45 Gy)
Experimental: Radiation + Androgen Suppression; Androgen Suppression Therapy x 6 months + Radiation	Radiation: Radiation; Consists of: Conformal Proton Radiation Dose: 2.5 Gy (RBE) five days a week in 28 treatments over 5.5-6.5 weeks (total dose: 70 Gy (RBE)); High Dose Radiation with IMRT alone: 1.8 Gy five days a week in 45 treatments over 9-10 weeks (total dose: 81 Gy); Intraoperative LDR Brachytherapy and IMRT: 100Gy Pad103 implant and IMRT 1.8 Gy five days a week in 25 treatments over 5-6 weeks (total dose: 45 Gy); Drug: Androgen Suppression Therapy; Androgen suppression will begin 8 - 10 weeks prior to the start of RT for a total of 6 (+/- 2) months. Luteinizing Hormone-Releasing Hormone (LHRH) agonist therapy will consist of analogs approved by the FDA (or by Health Canada for Canadian institutions); Other Names: leuprolide, goserelin, buserelin, or triptorelin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity Outcomes	To determine if androgen suppression along with radiation therapy will result in a higher freedom from failure (FFF) than radiation therapy without androgen suppression. Freedom from failure (FFF): The events for FFF will be the first occurrence of clinical failure (local recurrence, regional recurrence, or distant metastasis), biochemical failure by the Phoenix definition (PSA ≥ 2 ng/ml over the current nadir PSA) (45) discounting bounces per investigator discretion, or the start of salvage therapy including androgen suppression	after the initial 100 patients have had a median follow up of at least three years and then every year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of grade 2 or higher GU and GI toxicity	Assessment of grade 2 or higher GU and GI toxicity using CTCAE 4.0 criteria	At 6 months
Frequency and severity of GI and GU toxicity		At 3 years
Incidence of quality of life issues		At completion of radiation therapy
Incidence of Freedom from biochemical failure (FFBF)		At 5 years
Incidence of clinical failure: local and/or distant		At 5 years
Incidence of salvage Androgen Suppression use (SAD)		At 5 years
Incidence of progression free survival: using clinical, biochemical and SAD as events		At 5 years
Incidence of overall survival		At 5 years
Incidence of disease-specific survival		At 5 years
Correlate pathologic and radiologic findings with outcomes		At 5 years
Correlate PSA and free PSA levels with outcomes		At 5 years
Correlate testosterone levels and variation with proton therapy and outcomes		At 5 years
Prospectively collect information that will help to define dose-volume relationships of normal structures with acute and chronic toxicity		At 3 years

Collaborators and Investigators

• Sponsor: Proton Collaborative Group
• Investigators: Principal Investigator: Carlos Vargas, MD, Proton Collaborative Group

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 9, 2011
• First Submitted That Met QC Criteria: December 13, 2011
• First Posted (Estimated): December 15, 2011

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: radiation; Prostate; intermediate risk; proton
• 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; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Luteolytic Agents; Leuprolide; Goserelin; Triptorelin Pamoate; Androgens; Buserelin
• Other Study ID Numbers: GU003-10