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

• ClinicalTrials.gov Identifier: NCT01492972
• Recruitment Status: Recruiting
• First Posted: December 15, 2011
• Last Update Posted: April 4, 2023
• Sponsor: Proton Collaborative Group
• Information provided by (Responsible Party): Proton Collaborative Group

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Radiation: Radiation; Drug: Androgen Suppression Therapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Study of Image Guided Radiation Therapy With or Without Androgen Suppression for Intermediate Risk Adenocarcinoma of the Prostate
• Study Start Date: January 2012
• Estimated Primary Completion Date: December 2025

Arms and Interventions

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 Name: leuprolide, goserelin, buserelin, or triptorelin

Outcome Measures

Primary Outcome Measures :

1. Morbidity Outcomes [ Time Frame: after the initial 100 patients have had a median follow up of at least three years and then every year. ]

   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Matthew Morocco; 630-836-8670; mmorocco@pcgresearch.org

Locations

United States, Arizona

Mayo Clinic; Recruiting

Scottsdale, Arizona, United States, 85259-5499

Contact: : Clinical Trials Office - All Mayo Clinic Locations 855-776-0015 (toll free)

United States, Illinois

Northwestern Medicine Chicago Proton Center; Recruiting

Warrenville, Illinois, United States, 60555

Contact: Don Smith, MS, CCRC 630-933-7820 donald.smith3@nm.org

Principal Investigator: William Hartsell, MD

United States, Oklahoma

Oklahoma Proton Center; Recruiting

Oklahoma City, Oklahoma, United States, 73142

Contact: Jenny Washington, BSRT(T), CMD 405-773-6700 jenny.washington@okcproton.com

Principal Investigator: John Chang, MD

United States, Virginia

Hampton University Proton Therapy Institute; Recruiting

Hampton, Virginia, United States, 23666

Contact: Donna Sternberg, RN, BSN, OCN 757-251-6839 Donna.Sternberg@hamptonproton.org

Principal Investigator: Christopher Sinesi, MD

Sponsors and Collaborators

Proton Collaborative Group

Investigators

• Principal Investigator: Carlos Vargas, MD; Proton Collaborative Group

More Information

• Responsible Party: Proton Collaborative Group
• ClinicalTrials.gov Identifier: NCT01492972
• Other Study ID Numbers: GU003-10
• First Posted: December 15, 2011
• Last Update Posted: April 4, 2023
• Last Verified: April 2023

Keywords provided by Proton Collaborative Group:

Prostate; proton; radiation; intermediate risk

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Leuprolide; Goserelin; Triptorelin Pamoate; Buserelin; Androgens; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Contraceptive Agents, Hormonal