Clinical Trials /

Randomized MRI-Guided Prostate Boosts Via Initial Lattice Stereotactic vs Daily Moderately Hypofractionated Radiotherapy

NCT02307058

Description:

The BLaStM clinical trial extends the Phase I LEAD trial and compares the LEAD SBRT upfront technique for increasing dose to the MP-MRI defined GTVs, to the HEIGHT method of using a moderate hypofractionated simultaneous integrated boost to the MP-MRI defined GTVs through the course of radiotherapy. The hypothesis is that alternate mechanisms of cell death, including bystander effects, are put in place when doses above 8 Gy per fraction are used in a lattice on the first day of treatment and that the effects on local tumor eradication will be greater using this strategy.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Randomized MRI-Guided Prostate Boosts Via Initial Lattice Stereotactic vs Daily Moderately Hypofractionated Radiotherapy
  • Official Title: A Phase II Randomized Trial of MRI-Guided Prostate Boosts Via Initial Lattice Stereotactic vs Daily Moderately Hypofractionated Radiotherapy - The Miami BLaStM Trial

Clinical Trial IDs

  • ORG STUDY ID: 20140627
  • NCT ID: NCT02307058

Conditions

  • Prostate Cancer

Purpose

The BLaStM clinical trial extends the Phase I LEAD trial and compares the LEAD SBRT upfront technique for increasing dose to the MP-MRI defined GTVs, to the HEIGHT method of using a moderate hypofractionated simultaneous integrated boost to the MP-MRI defined GTVs through the course of radiotherapy. The hypothesis is that alternate mechanisms of cell death, including bystander effects, are put in place when doses above 8 Gy per fraction are used in a lattice on the first day of treatment and that the effects on local tumor eradication will be greater using this strategy.

Detailed Description

      Radiotherapy (RT) is a commonly applied primary (initial definitive) treatment alternative to
      prostatectomy that allows for preservation of anatomy and the potential for improved
      functional outcome with better tumor targeting and normal tissue sparing. About 30-50% of men
      ultimately develop biochemical failure (BF) after RT, depending on risk factors. Persistence
      of disease in the dominant lesion is indicated to be a common mechanism responsible for
      progression. Prostate cancer has a long natural history. BF typically precedes clinical
      progression to metastasis by many years and local persistence has been implicated. While
      survival at 10 years is high overall, quality of life is affected by failure of any kind.
      Pathologic complete response (PathCR) by standard ultrasound guided systematic prostate
      biopsies at 2-3 years after RT is the strongest post-treatment (post-Tx) predictor of patient
      outcome yet identified. Multiparametric-MRI (MP-MRI) parameters identify dominant tumor areas
      in the prostate with a fairly high sensitivity and specificity, and MP-MRI directed biopsies
      should, therefore, further strengthen the association between prostate biopsy results and
      patient outcome.

      The proposed research compares two previously explored methods (LEAD and HEIGHT) for
      escalating dose to MP-MRI defined prostate regions directly and addresses the goals of 1)
      improving local control via targeted radiotherapy (RT) dose escalation to the MP-MRI defined
      high risk (dominant) tumor areas using PathCR based on MP-MRI-directed biopsies at 2-2.5yr
      after treatment as the primary endpoint; 2) preserving quality of life by minimizing dose to
      the nearby organs at risk around the prostate; and 3) establishing the relationship of pre-
      and serial post-Tx MP-MRI parameters to PathCR.
    

Trial Arms

NameTypeDescriptionInterventions
LEAD RTActive ComparatorLEAD: Lattice Extreme Ablative Dose, a form of MRI-Targeted Stereotactic Lattice radiotherapy; International Prostate Symptom Score, Memorial Anxiety Scale for Prostate Cancer patients, and Expanded Prostate Cancer Index Composite-Short Form 12 (EPIC SF-12) questionnaires
    HEIGHT RTActive ComparatorHEIGHT: Hypofractionated Extended Image-Guided Highly Targeted, a form of MRI-Targeted Moderate Hypofractionation; International Prostate Symptom Score, Memorial Anxiety Scale for Prostate Cancer patients, and Expanded Prostate Cancer Index Composite-Short Form 12 (EPIC SF-12) questionnaires.

      Eligibility Criteria

              Eligibility Criteria:
      
                -  A. Biopsy confirmed adenocarcinoma (including ductal) of the prostate.
      
                -  B. T1-T3 disease based on digital rectal exam.
      
                -  C. No evidence of metastasis by any clinical criteria or available radiographic tests
                   (N0M0 by clinical or imaging criteria).
      
                -  D. Gleason score 6-10.
      
                -  E. Androgen deprivation therapy (ADT) is at the discretion of the treating physician;
                   but, must be decided (none, short-term or long-term as counted from the luteinizing
                   hormone-releasing hormone (LHRH) agonist or antagonist injection) prior to enrollment.
                   An anti-androgen (e.g., bicalutamide at 50 mg per day po) is recommended to start
                   prior to LHRH agonist injection (not recommended for LHRH antagonist injection) and is
                   recommended to not be administered for more than 4 months. If ADT is planned, the
                   following restrictions apply:
      
                     -  i. It may be initiated no more than 3 months prior to the signing of consent
      
                     -  ii. It must be started prior to the start of radiotherapy and
      
                     -  iii. The total length planned must be ≤ 30 months
      
                -  F. Prostate-specific Antigen (PSA) ≤ 100 ng/mL within (+/-) 4 months of signing of
                   consent. If PSA was above 100 and drops to ≤ 100 with antibiotics, this is acceptable
                   for enrollment.
      
                -  G. Subjects with T3 disease based on digital rectal exam (DRE), Gleason 8-10 or a PSA
                   of >15 ng/ml, should have a bone scan within (+/-) 4 months of signing of consent that
                   is without evidence of metastasis. A questionable bone scan is acceptable if
                   additional imaging studies (e.g., plain x-rays, CT, or MRI) do not confirm for
                   metastasis.
      
                -  H. Suspicious peripheral zone or central gland lesion on MP-MRI
      
                     -  i. Peripheral zone: Distinct lesion on dynamic contrast-enhanced MRI (DCE-MRI)
                        with early enhancement and later washout (Note: contrast not required for
                        enrollment), and/or distinct lesion on the ADC map (Value <1000).
      
                     -  ii. Central gland: A suspicious central gland lesion on MP-MRI must have a
                        distinct lesion on the apparent diffusion coefficient (ADC) map (Value <1000)
      
                -  I. No previous pelvic radiotherapy.
      
                -  J. No previous history of radical/total prostatectomy (suprapubic prostatectomy is
                   acceptable).
      
                -  K. No concurrent, active malignancy, other than nonmetastatic skin cancer or early
                   stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic
                   lymphoma). If a prior malignancy is in remission for ≥ 5 years then the patient is
                   eligible.
      
                -  L. Ability to understand and the willingness to sign a written informed consent
                   document.
      
                -  M. Zubrod performance status ≤ 2. (Karnofsky or Eastern Cooperative Oncology Group
                   (ECOG) performance status may be used to estimate Zubrod).
      
                -  N. Willingness to fill out quality of life/psychosocial forms.
      
                -  O. Age ≥ 35 and ≤ 85 years at signing of consent.
            
      Maximum Eligible Age:85 Years
      Minimum Eligible Age:35 Years
      Eligible Gender:Male
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Rate of Prostate Tumor Pathologic Complete Response (PathCR) between subjects on LEAD RT (Arm 1) and HEIGHT RT (Arm 2)
      Time Frame:2 - 2.5 Years after completion of all planned treatment
      Safety Issue:
      Description:To compare the rate of prostate tumor pathologic complete response (PathCR) by prostate biopsies at 2-2.5 years after completion of all planned treatment (radiotherapy and androgen deprivation therapy) between two multiparametric MRI (MP-MRI)-defined tumor radiotherapy boost methods (from the Miami LEAD and HEIGHT trials).

      Secondary Outcome Measures

      Measure:Correlation between Pathologic Complete Response (PathCR) and Changes in serial post-RT MRIs
      Time Frame:3 months post-RT, 9-months post-RT, within 3 months of 2-2.5 post-treatment biopsy
      Safety Issue:
      Description:To establish the relationship between PathCR and changes in serial post-RT MRI's obtained at 3 months and 9 months after RT, and within 3 months prior to the primary endpoint post-treatment prostate biopsy at 2.0-2.5 yr after completion of all therapy.
      Measure:Number of subjects experiencing adverse events
      Time Frame:From Enrollment to 2 years Post-treatment
      Safety Issue:
      Description:To evaluate and compare acute and late toxicity.
      Measure:Comparison of Subjects' pre-treatment and post-treatment Quality of Life
      Time Frame:From Enrollment to 5.25 years Post-treatment
      Safety Issue:
      Description:To compare pretreatment and posttreatment Health-Related Quality of Life (HRQOL) between the arms, using quality of life questionnaires at protocol defined intervals.
      Measure:Change in gene/biomarker expression in different MP-MRI prostate tumor regions
      Time Frame:Up to 5.25 years
      Safety Issue:
      Description:To quantify gene/biomarker expression in different MP-MRI prostate tumor regions (habitats) and to relate developed habitat signatures to MP-MRI changes, PathCR and other secondary clinical outcome endpoints.
      Measure:Rate of biochemical failure, clinical failure, cause-specific mortality and overall mortality in subjects.
      Time Frame:Up to 5.25 years
      Safety Issue:
      Description:To determine biochemical failure, clinical (distant metastasis and overall) failure, cause specific mortality and overall mortality rates.
      Measure:Change in number, viability and gene expression of circulating tumor cells pre-treatment and post-treatment at protocol defined intervals
      Time Frame:Pre-Treatment up up to within 3 months of 2-2.5 yr post-treatment biopsy
      Safety Issue:
      Description:To evaluate the numbers, viability, and gene expression of circulating tumor cells (CTC's) pretreatment and at different posttreatment intervals (same as for post-treatment MRIs).

      Details

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

      Trial Keywords

      • Prostate Cancer

      Last Updated

      November 13, 2019