Clinical trial NCT00214097: Phase I/II Hypofractionated Radiotherapy for Prostate Cancer
Official title: Phase I/II Trial Examining Dose-per-Fraction Escalation Using Intensity Modulated Radiation Therapy in the Treatment of Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2005-09-21
Enrollment: 347
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: dose escalation, 3 possible dose groups, with one Phase II group based on MTD.

Per protocol, while waiting for safety data to mature for escalation, protocol permitted enrollment to continue on last dose that was already proven safe. Thus Arms one and two have more than 50 subjects each.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experience Grade 3 or Higher Acute Toxicities
timeFrame: 90 days post radiation treatment
measure: Number of Subjects Experiencing Grade 2 or Higher Late Rectal Toxicities at Any Time During Follow Up
timeFrame: from 90 days post XRT through last follow-up visit (up to 3 years)
Secondary outcomes:
measure: Biochemical Progression-free Survival Based on PSA Surveillance
timeFrame: up to 15 years from enrollment
measure: Fox Chase Bowel Survey at Baseline and 3 Years
timeFrame: Baseline and 3 years
measure: Fox Chase Bladder Survey at Baseline and 3 Years
timeFrame: Baseline and 3 years
measure: International Index of Erectile Function (IIEF) Score at Baseline and 3 Years
timeFrame: Baseline and 3 years
measure: Spritzer Quality of Life Index (SQLI) at Baseline and 3 Years
timeFrame: Baseline and 3 years
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Mark Ritter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.