Clinical Trials /

Dose-Escalated Proton Radiation Therapy for High-Risk Prostate Cancer

NCT03624660

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Dose-Escalated Proton Radiation Therapy for High-Risk Prostate Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IRB201800933
  • SECONDARY ID: UFPTI 1712-PR11
  • SECONDARY ID: OCR17697
  • NCT ID: NCT03624660

Conditions

  • Adenocarcinoma of the Prostate

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
HR-A (High-risk A)ExperimentalProstate 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.
    HR-B (High-risk B)ExperimentalProstate, 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.
      HR-C (High-risk C)ExperimentalProstate, entire seminal vesicles, and pelvic nodes: 2 cobalt gray equivalent per fraction to a total dose of 46 cobalt gray equivalent. Prostate and entire involved 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.

        Eligibility Criteria

                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, 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).
              
        Maximum Eligible Age:100 Years
        Minimum Eligible Age:18 Years
        Eligible Gender:Male
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Cumulative rate of biochemical failure at 5 years after the end of treatment.
        Time Frame:5 years after the end of radiation therapy
        Safety Issue:
        Description: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.

        Secondary Outcome Measures

        Measure: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
        Safety Issue:
        Description: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.
        Measure: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
        Safety Issue:
        Description: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.
        Measure: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
        Safety Issue:
        Description: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.
        Measure:Assessment of overall and disease-free survival
        Time Frame:5 years after the end of radiation therapy
        Safety Issue:
        Description: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.
        Measure:Assessment of local persistence or local recurrence
        Time Frame:5 years after the end of radiation therapy
        Safety Issue:
        Description: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.
        Measure:Rate of distant metastases five years after end of radiation therapy
        Time Frame:5 years after the end of radiation therapy
        Safety Issue:
        Description: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.

        Details

        Phase:N/A
        Primary Purpose:Interventional
        Overall Status:Recruiting
        Lead Sponsor:University of Florida

        Trial Keywords

        • High-risk
        • Prostate cancer
        • Proton Radiation
        • Dose-escalated
        • Hypofractionation
        • Simultaneous Integrated Boost (SIB)
        • Intraprostatic Tumor (IPT)
        • Proton Therapy (PT)
        • Androgen Deprivation Therapy (ADT)
        • Magnetic Resonance Imaging (MRI)

        Last Updated

        August 22, 2019