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Dose-Escalated Proton Radiation Therapy for High-Risk Prostate Cancer (PR11)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03624660
Recruitment Status : Recruiting
First Posted : August 10, 2018
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE July 23, 2018
First Posted Date  ICMJE August 10, 2018
Last Update Posted Date January 9, 2020
Actual Study Start Date  ICMJE September 24, 2018
Estimated Primary Completion Date September 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
Cumulative rate of biochemical failure at 5 years after the end of treatment. [ Time Frame: 5 years after the end of radiation therapy ]
Biochemical failure will be defined based on the Phoenix definition. Biochemical failure has occurred if the post-treatment prostate-specific antigen (PSA) on at least two occasions rose more than 2 ng/ml above the PSA nadir. Rate of biochemical failure will be measured at 5 years after the end of treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
  • Cumulative rate of acute toxicity observed between day 1 of treatment and 90 days after treatment. [ Time Frame: 90 days after the end of radiation therapy ]
    Assess physician-graded, severe (Grade 3-4), acute (early, within 90 days of treatment) genitourinary and gastrointestinal toxicity rates based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
  • Cumulative rate of late toxicity observed between 90 days and 5 years after end of treatment. [ Time Frame: 60 months after the end of radiation therapy ]
    Assess physician-graded, severe (Grade 3-4), late (beginning 90 or more days after treatment), cumulative 5 year genitourinary and gastrointestinal toxicity rates based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
  • Rate of change in sexual, bowel, and urinary function from baseline measurement to 5 years after end of treatment. [ Time Frame: Rate of change between baseline measurement and 5 years end of radiation therapy ]
    Assess changes in patient-reported quality of life before and after treatment according to The International Index of Erectile Function (IIEF-5/IIEF-5m) which measures sexual function and the effect of radiation therapy; The International Prostate Symptom Score (IPSS) which measures urinary function and the effect of radiation therapy; and The Expanded Prostate Cancer Index Composite (EPIC) which measures different areas that may be affected by prostate cancer or its treatment.
  • Assessment of overall and disease-free survival [ Time Frame: 5 years after the end of radiation therapy ]
    Assess the overall survival, defined as the time from the start of treatment to the date of death of any cause, if data is available, at 5 years. Also, cause-specific survival will be calculated.
  • Assessment of local persistence or local recurrence [ Time Frame: 5 years after the end of radiation therapy ]
    Assess local persistence or local recurrence of prostate cancer at 5 years. Local persistence is defined as the failure of the original abnormal tumor mass seen on cross sectional imaging and/or found on digital rectal exam to resolve in patients who also had a poor PSA response with a PSA nadir greater than 1 ng/mL. Local recurrence is defined as the development of any new abnormal prostate mass on cross sectional imaging or on digital rectal exam with previous exams or imaging showing no mass in the area prior to radiation therapy or after initial treatment.
  • Rate of distant metastases five years after end of radiation therapy [ Time Frame: 5 years after the end of radiation therapy ]
    Assess the cumulative rate development of distant metastasis up to 5 years after end of radiation. This will be an aggregate binary, yes/no response based on evidence acquired from sources including CT scan, bone scan, and/or PET/CT scan.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-Escalated Proton Radiation Therapy for High-Risk Prostate Cancer
Official Title  ICMJE A Phase II Study of Dose-Escalated Proton-Based Radiation Therapy Delivered With a Simultaneous Integrated Boost (SIB) to Intraprostatic Tumors (IPT) Visible on Pretreatment Magnetic Resonance Image
Brief Summary The purpose of this research study is to determine if dose-escalated proton radiation therapy is a good way to treat high-risk prostate cancer. The study features hypofractionation and a simultaneous integrated boost to the magnetic resonance imaging (MRI) identified intraprostatic tumor (IPT) as a method of dose-escalating radiation therapy. The study will include patients with high-risk prostate cancer who are at the highest risk for recurrence. Radiation therapy will be delivered over the course of 8-9 weeks. Additionally, androgen deprivation therapy (ADT) will be started 8-10 weeks prior to starting radiation and continued for a total of 18 months if the patient decides to receive ADT.
Detailed Description

Prostate cancer is the most common noncutaneous cancer among men in the United States. The purpose of this research study is to determine if dose-escalated proton radiation therapy is a good way to treat high-risk prostate cancer.

Proton therapy (PT) is a type of ionizing radiation therapy that reduces the dose of excess radiation delivered to normal tissues. By escalating the radiation dose just to the area of the known tumor within the prostate, one could potentially reduce the amount of excess radiation delivered to surrounding organs.This reduction in dose would improve the therapeutic ratio by improving disease control while minimizing the risk for additional toxicity.

In an effort to take advantage of dose escalation's potential for improving disease control but also to limit toxicity, the use of advanced imaging to identify prostate cancer and provide a focal radiation boost to the area have proven to be useful. Recent advances in MRI have made it the most promising technique in identifying and targeting IPTs, improving both cancer control rates and decreasing toxicity.

The study features hypofractionation and a simultaneous integrated boost to the MRI identified intraprostatic tumor (IPT) as a method of dose-escalating radiation therapy. The study will include patients with high-risk prostate cancer who are at the highest risk for recurrence. Radiation therapy will be delivered over the course of 8-9 weeks. Additionally, androgen deprivation therapy (ADT) will be started 8-10 weeks prior to starting radiation and continued for a total of 18 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients will be assigned to treatment group according to their lymph node risk.

3 treatment groups:

  • HR-A: Patients with <25% risk of positive pelvic nodes, without posterior extracapsular extension and negative for seminal vesicle invasion on exam pretreatment diagnostic MRI.
  • HR-B: Patient with ≥ 25% risk of positive pelvic nodes, without posterior extracapsular extension and negative for seminal vesicle invasion.
  • HR-C: Patients with seminal vesicle invasion.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adenocarcinoma of the Prostate
Intervention  ICMJE
  • Radiation: HR-A

    The prostate and proximal seminal vesicles will be treated to 2 cobalt gray equivalent per fraction for 39 fractions for a total of 78 cobalt gray equivalent.

    Simultaneous integrated boost to the IPT will be delivered to 2.2 cobalt gray equivalent per fraction for 39 fractions for a total of 85.8 cobalt gray equivalent.

    Treatment will be given once a day, approximately 5 treatments per week (Monday- Friday), over 8-9 weeks.

    Other Name: Proton Radiation
  • Radiation: HR-B

    The prostate, proximal seminal vesicles, and pelvic nodes will be treated to 2 cobalt gray equivalent per fraction for 23 fractions for a total of 46 cobalt gray equivalent.

    The prostate and proximal seminal vesicles will be treated to an additional 2 cobalt gray equivalent per fraction for 16 fractions for a total of 32 cobalt gray equivalent.

    Simultaneous integrated boost to the IPT will be delivered to 2.2 cobalt gray equivalent per fraction for 39 fractions for a total of 85.8 cobalt gray equivalent.

    Treatment will be given once a day, approximately 5 treatments per week (Monday- Friday), over 8-9 weeks.

    Other Name: Proton Radiation
  • Radiation: HR-C

    The prostate, entire seminal vesicles, and pelvic nodes will be treated to 2 cobalt gray equivalent per fraction for 23 fractions for a total of 46 cobalt gray equivalent.

    The prostate and entire seminal vesicles will be treated to an additional 2 cobalt gray equivalent per fraction for 7 fractions for a total of 14 cobalt gray equivalent.

    The prostate, entire involved seminal vesicle, and at least the proximal seminal vesicle on the uninvolved side will be treated to an additional 2 cobalt gray equivalent per fraction for 9 fractions for a total of 18 cobalt gray equivalent.

    Simultaneous integrated boost to the IPT will be delivered to 2.2 cobalt gray equivalent per fraction for 39 fractions for a total of 85.8 cobalt gray equivalent.

    Treatment will be given once a day, approximately 5 treatments per week (Monday- Friday), over 8-9 weeks.

    Other Name: Proton Radiation
Study Arms  ICMJE
  • Experimental: HR-A (High-risk A)
    • Prostate and proximal seminal vesicles: 2 cobalt gray equivalent per fraction to a total dose of 78 cobalt gray equivalent.
    • Simultaneous integrated boost to the IPT: 2.2 cobalt gray equivalent per fraction to a total dose of 85.8 cobalt gray equivalent.
    Intervention: Radiation: HR-A
  • Experimental: HR-B (High-risk B)
    • Prostate, proximal seminal vesicles, and pelvic nodes: 2 cobalt gray equivalent per fraction to a total does of 46 cobalt gray equivalent.
    • Prostate and proximal seminal vesicles: 2 cobalt gray equivalent per fraction to a total dose of 32 cobalt gray equivalent.
    • Simultaneous integrated boost to the IPT: 2.2 cobalt gray equivalent per fraction to a total dose of 85.8 cobalt gray equivalent.
    Intervention: Radiation: HR-B
  • Experimental: HR-C (High-risk C)
    • Prostate, entire seminal vesicles, and pelvic nodes: 2 cobalt gray equivalent per fraction to a total dose of 46 cobalt gray equivalent.
    • Prostate and entire seminal vesicles: 2 cobalt gray equivalent per fraction to a total dose of 14 cobalt gray equivalent.
    • Prostate, entire involved seminal vesicle, and at least the proximal seminal vesicle on uninvolved side: 2 cobalt gray equivalent per fraction to a total dose of 18 cobalt gray equivalent.
    • Simultaneous integrated boost to the IPT: 2.2 cobalt gray equivalent per fraction to a total dose of 85.8 cobalt gray equivalent.
    Intervention: Radiation: HR-C
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 22, 2019)
100
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2018)
88
Estimated Study Completion Date  ICMJE September 2028
Estimated Primary Completion Date September 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient must give study-specific informed consent on an IRB-approved consent prior to any research related procedures or study treatment.
  • Patient must be at least 18 years at the time of consent.
  • Adenocarcinoma of the prostate with AJCC Clinical Stage T1to T3b disease with histological evaluation via biopsy or repeat biopsy within 12 months prior to registration.
  • Patients must undergo a pretreatment diagnostic MRI of the prostate on a 1.5T to 3T Tesla machine within 6 months prior to study registration.
  • A focal IPT must be visible on MRI within the prostate and/or seminal vesicles and this MRI must be obtained within 6 months of planning CT scan.
  • A biopsy of the dominant lesion is recommended but not required. If an ultrasound guided sextant biopsy was positive for prostatic adenocarcinoma in the area of the MRI identified intraprostatic lesion, this will be acceptable and another guided biopsy targeting the MRI identified disease will not be necessary.
  • Patients with at least one of the following high-risk factors: cT3a-T3b OR Gleason 9-10 OR PSA > 30 OR more than 1 high-risk factors must be present: clinical stage of T3, Gleason score 8-10, or PSA 20 ng/ml or greater.
  • Hemoglobin must be ≥ 10 g/ml within 4 months prior to registration.
  • Zubrod performance status must be 0-1 within 4 months prior to registration.
  • If patient has child-producing potential, they must be willing to use medically acceptable contraception during treatment and must be advised to use it for at least 1 year thereafter. This is not applicable if the patient is not sexually active or has had a vasectomy.
  • Patients must be able to start treatment within 16 weeks of registration.

Exclusion Criteria:

  • T4 prostate disease on CT, MRI, or physical exam.
  • Patients unable to undergo MRI of the prostate.
  • Patients with a greater than 25% change in prostate volume from the pretreatment MRI of the prostate demonstrating the IPT and the treatment planning MRI. Patients in this case must undergo a repeat diagnostic MRI on a 1.5T to 3.0T Tesla machine and an IPT must still be visible.
  • Patients with posterior or posterolateral extracapsular extension of prostate cancer. If this is present, it must resolve on diagnostic MRI after 2 to 3 months of neoadjuvant androgen deprivation therapy prior to enrollment.
  • IPT that is more than 75% of the prostate volume when measured on the CT simulation scan.
  • Evidence of distant metastasis (M1).
  • Patients with positive nodes on cross-sectional imaging.
  • Previous prostate cancer local treatment including prostatectomy, hyperthermia, high intensity focused ultrasound, brachytherapy, external-beam radiation therapy, and/or cryotherapy.
  • Prior pelvic radiation therapy.
  • No prior myocardial infarction within the last 6 months, severe congestive heart failure, or end stage renal disease.
  • Active inflammatory bowel disease (diverticulitis, Crohn's disease, ulcerative colitis) affecting the rectum.
  • Bilateral hip replacement
  • Prior intrapelvic surgery. This includes the following:

    • Bladder surgery
    • Transrectal or rectal surgery other than prostate biopsy
    • Polypectomy or hemorrhoid removal or banding
  • Prior transurethral resection of the prostate (TURP) or laser ablation for benign prostatic hyperplasia (BPH).
  • Patients receiving continuous and current anticoagulation with warfarin sodium (Coumadin), heparin sodium, clopidogrel bisulfate (Plavix), dabigatran etexilate mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), enoxaparin sodium (Lovenox), prasugrel (Effient), ticagrelor (Brilinta), aspirin/er dipyridamole (Aggrenox), or fondaparinux sodium (Arixtra).
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Prostate cancer is gender-specific. Biological males only.
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Intake Coordinator 877-686-6009 jinpark@floridaproton.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03624660
Other Study ID Numbers  ICMJE IRB201800933
UFPTI 1712-PR11 ( Other Identifier: Proton Therapy Institute ID )
OCR17697 ( Other Identifier: Universiy of Florida )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Curtis M Bryant, MD, MPH University of Florida Health Proton Therapy Institute
PRS Account University of Florida
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP