Phase I/II Hypofractionated Radiotherapy for Prostate Cancer

Phase I/II Trial Examining Dose-per-Fraction Escalation Using Intensity Modulated Radiation Therapy in the Treatment of Prostate Cancer

The purpose of this study is to examine the clinical feasibility of using Intensity-modulated radiation therapy (IMRT) combined with daily pretreatment prostate localization to deliver increasingly hypofractionated treatment courses. Progressively larger fraction sizes will be delivered in a phase I design based on both acute and long-term tolerances to the treatment. The dose-per-fraction escalation design utilizes schemas that maintain an isoeffective dose for late effects, while predicting that tumor control will actually improve. The delivery of fewer, larger fractions of radiation, if proven effective and safe, would result in significant cost saving and more efficient use of resources. Phase II will commence with Maximum Tolerated Dose (MTD) finding with up to 200 additional patients being enrolled during this phase of the study.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 347
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Histologically proven adenocarcinoma of the prostate.

• Stage ≤ T2b disease, as defined by 1997 American Joint Committee on Cancer (AJCC) classification
• Predicted risk of lymph node involvement (by standard nomograms) of 15% or less (24), OR histologically negative pelvic nodes
• Gleason score ≤ 7
• No evidence of distant metastasis
• Age 18+
• Informed consent signed in accordance with institutional protocol
• Pretreatment evaluations must be completed as specified in Section 7.0.
• ECOG performance status 0-1
• No previous or concurrent cancers, other than localized basal cell or squamous cell skin carcinoma, unless continually disease free for at least 5 years
• No prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy
• Gonadotropin-releasing hormone agonist (GnRH-a) use permitted (maximum of 6 months duration). Anti-androgen therapy permitted concurrently with GnRH-a.
• No previous or concurrent cytotoxic chemotherapy
• No radical surgery or cryosurgery for prostate cancer
• The absence of any co-morbid medical condition which would constitute a contraindication for radical radiotherapy
• The absence of serious concurrent illness of psychological, familial, sociological, geographical or other concomitant conditions which do not permit adequate follow-up and compliance with the study protocol.
• No current use of anticoagulation therapy, other than aspirin.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Level 1; 64.7 Gy/22 fractions of 2.94 Gy	Radiation: Radiotherapy; Daily radiation to prescribed dose
Experimental: Level 2; 58.08 Gy/16 fractions of 3.63 Gy	Radiation: Radiotherapy; Daily radiation to prescribed dose
Experimental: Level 3; 51.6 Gy/12 fractions of 4.3 Gy	Radiation: Radiotherapy; Daily radiation to prescribed dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience Grade 3 or Higher Acute Toxicities	To evaluate acute tolerances to dose-per-fraction escalation in the treatment of prostate cancer using optimized treatment of Intensity-modulated radiation therapy (IMRT), daily rectal balloon displacement, and transabdominal ultrasound localization of the prostate. For toxicities observed within the first 10 patients at each hypofractionation level, ≥20% acute grade 3 or higher GI or genitourinary (GU) toxicity will constitute a threshold toxicity level and will dictate a decrease in frequency of treatment by one treatment per week. Maximum tolerated dose is reached if 20% of participants experience acute toxicities grade 3 or higher.	90 days post radiation treatment
Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up	To evaluate late radiation toxicities to dose-per fraction escalation in the treatment of prostate	from 90 days post XRT through last follow-up visit (up to 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Progression-free Survival Based on PSA Surveillance	Patients will be considered to be without biochemical recurrence if either the Prostate-specific antigen (PSA) is still declining or the PSA nadir has been reached and is below 1.0ng/ml	up to 15 years from enrollment
Fox Chase Bowel Survey at Baseline and 3 Years	The Fox Chase Bowel/Bladder survey was divided into two sections: Bowel (questions 1 to 14, N=14) and Bladder (questions 19, and 21 to 30, N=11). To facilitate analysis, Bowel and Bladder scores for each section were rescaled to a total score of between 0 - 100, where higher scores indicated better Quality of Life (QoL). Results for the Bowel Section are reported here.	Baseline and 3 years
Fox Chase Bladder Survey at Baseline and 3 Years	The Fox Chase Bowel/Bladder survey was divided into two sections: Bowel (questions 1 to 14, N=14) and Bladder (questions 19, and 21 to 30, N=11). To facilitate analysis, Bowel and Bladder scores for each section were rescaled to a total score of between 0 - 100, where higher scores indicated better Quality of Life. Results for the Bladder Section are reported here.	Baseline and 3 years
International Index of Erectile Function (IIEF) Score at Baseline and 3 Years	The IIEF is a 15-item survey where 9-items are scored 0-5 and 6-items are scored 1-5 with a total range of 6-75. The standard scoring mechanism was used for IIEF, where the QoL items corresponded to the following domains: erectile function (score range 1-30), orgasmic function (score range 1-10), sexual desire (score range 2-10), intercourse satisfaction (score range 0-15), and overall satisfaction (score range 2-10). Higher numbers indicate increased QoL.	Baseline and 3 years
Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years	The SQLI is composed of five items (activity, daily living, health, support, outlook) scored utilizing a numerical scale of 0-2. Standard scoring was also used for the SQLI survey (total score range 0-10) where higher score indicate increased QoL.	Baseline and 3 years

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Mark Ritter, MD, PhD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Brower JV, Forman JD, Kupelian PA, Petereit DG, Gondi V, Lawton CA, Anger N, Saha S, Chappell R, Ritter MA. Quality of life outcomes from a dose-per-fraction escalation trial of hypofractionation in prostate cancer. Radiother Oncol. 2016 Jan;118(1):99-104. doi: 10.1016/j.radonc.2015.12.018. Epub 2016 Jan 2.

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2002
• Primary Completion (Actual): August 21, 2017
• Study Completion (Actual): August 21, 2017

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Actual): November 25, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: RO02803; A533300 (Other Identifier: UW Madison); SMPH/HUMAN ONCOLOGY (Other Identifier: UW Madison); NCI (P01 CA88960); 2002-322 (Other Identifier: Institutional Review Board)