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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Alan Pollack, University of Miami
Sponsor:
Information provided by (Responsible Party):
Alan Pollack, University of Miami
ClinicalTrials.gov Identifier:
NCT02307058
First received: December 1, 2014
Last updated: April 10, 2017
Last verified: April 2017
  Purpose
The BLaStM clinical trial extends the Phase I LEAD trial and compares the LEAD 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 and that the effects on local tumor eradication will be greater using this strategy.

Condition Intervention
Prostate Cancer Radiation: LEAD RT Radiation: HEIGHT RT Behavioral: International Prostate Symptom Score Behavioral: Memorial Anxiety Scale for Prostate Cancer patients Behavioral: Expanded Prostate Cancer Index Composite-Short Form 12

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Alan Pollack, University of Miami:

Primary Outcome Measures:
  • 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 ]
    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:
  • 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 ]
    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.

  • Number of subjects experiencing adverse events [ Time Frame: From Enrollment to 2 years Post-treatment ]
    To evaluate and compare acute and late toxicity.

  • Comparison of Subjects' pre-treatment and post-treatment Quality of Life [ Time Frame: From Enrollment to 5.25 years Post-treatment ]
    To compare pretreatment and posttreatment Health-Related Quality of Life (HRQOL) between the arms, using quality of life questionnaires at protocol defined intervals.

  • Change in gene/biomarker expression in different MP-MRI prostate tumor regions [ Time Frame: Up to 5.25 years ]
    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.

  • Rate of biochemical failure, clinical failure, cause-specific mortality and overall mortality in subjects. [ Time Frame: Up to 5.25 years ]
    To determine biochemical failure, clinical (distant metastasis and overall) failure, cause specific mortality and overall mortality rates.

  • 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 ]
    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).


Estimated Enrollment: 164
Actual Study Start Date: February 5, 2015
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LEAD RT
LEAD: Lattice Extreme Ablative Dose, a form of 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
Radiation: LEAD RT
LEAD RT: Radiotherapy will begin within two months of fiducial marker placement. The therapy will consist of 39 fractions over ~8 weeks. The multiparametric-MRI (MP-MRI) defined gross tumor volume (GTV) will receive 12-14 Gy on the first day of treatment and then the prostate plus proximal seminal vesicles (SVs, usually 7-10 mm and/or <= 50%, whichever is less), the CTV1, will receive 76 Gy in 38 fractions (Fxs) at 2.0 Gy per Fx. For High Risk patients, the distal SVs (CTV2) may be treated to 56 Gy in 38 Fxs or full IMRT dose of 76 Gy, and the pelvic lymph nodes (CTV3) may be treated to 56 Gy in 38 Fxs.
Other Name: Stereotactic Lattice Radiation Therapy
Behavioral: International Prostate Symptom Score
International Prostate Symptom Score (IPSS) will be administered pretreatment, at the end of treatment and at each follow-up visit.
Other Name: IPSS
Behavioral: Memorial Anxiety Scale for Prostate Cancer patients
Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Quality of Life questionnaire - Recommended after enrollment and prior to fiducial marker placement, as well as during the last week of treatment, and post-RT at 3 mo, 9 mo and then yearly to 5.25 years.
Other Name: MAX-PC
Behavioral: Expanded Prostate Cancer Index Composite-Short Form 12
Expanded Prostate Cancer Index Composite-Short Form 12 (EPIC SF-12) Quality of Life questionnaire - Recommended after enrollment and prior to fiducial marker placement, as well as during the last week of treatment, and post-RT at 3 mo, 9 mo and then yearly to 5.25 years.
Other Name: EPIC SF-12
Active Comparator: HEIGHT RT
HEIGHT: Hypofractionated Extended Image-Guided Highly Targeted, a form of 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.
Radiation: HEIGHT RT
HEIGHT RT: Radiotherapy will begin within two months of fiducial marker placement. The therapy will consist of 38 fractions over ~7.5 weeks. The MRI defined GTV will receive a higher dose per day than the clinical tumor volume (CTV) by dose painting. The GTV will receive an absolute dose of 91.2 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 98.5 Gy in 2.0 Gy fractions. The prostate plus proximal seminal vesicles CTV1 will receive 76 Gy in 38 fractions (Fxs) at 2.0 Gy per Fx. For High Risk patients, the distal SVs (CTV2) may be treated to 56 Gy in 38 Fxs or full IMRT dose of 76 Gy, and the pelvic lymph nodes (CTV3) may be treated to 56 Gy in 38 Fxs.
Other Name: Moderate Hypofractionation Radiation Therapy
Behavioral: International Prostate Symptom Score
International Prostate Symptom Score (IPSS) will be administered pretreatment, at the end of treatment and at each follow-up visit.
Other Name: IPSS
Behavioral: Memorial Anxiety Scale for Prostate Cancer patients
Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Quality of Life questionnaire - Recommended after enrollment and prior to fiducial marker placement, as well as during the last week of treatment, and post-RT at 3 mo, 9 mo and then yearly to 5.25 years.
Other Name: MAX-PC
Behavioral: Expanded Prostate Cancer Index Composite-Short Form 12
Expanded Prostate Cancer Index Composite-Short Form 12 (EPIC SF-12) Quality of Life questionnaire - Recommended after enrollment and prior to fiducial marker placement, as well as during the last week of treatment, and post-RT at 3 mo, 9 mo and then yearly to 5.25 years.
Other Name: EPIC SF-12

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. 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.

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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. However if it 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02307058

Contacts
Contact: Alan Pollack, MD, PhD 305-243-4916 apollack@med.miami.edu
Contact: Marinellie Vega mvega@med.miami.edu

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Alan Pollack, MD, PhD    305-243-4916    apollack@med.miami.edu   
Contact: Marinellie Vega    305-243-6809    mvega@med.miami.edu   
Principal Investigator: Alan Pollack, MD         
Principal Investigator: Matthew Abramowitz, MD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Alan Pollack, MD, PhD University of Miami
  More Information

Responsible Party: Alan Pollack, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT02307058     History of Changes
Other Study ID Numbers: 20140627
Study First Received: December 1, 2014
Last Updated: April 10, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Some data after completion of the trial and publication of the primary endpoint. Additional data after publication of the secondary endpoints.

Keywords provided by Alan Pollack, University of Miami:
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on June 22, 2017