The purpose of this research study is to learn about: 1) improving control of prostate cancer
using an extra high dose radiation treatment to the MRI defined high risk tumor areas, in
addition to the standard radiation treatment to the rest of the prostate; 2) preserving
quality of life by reducing dose to the nearby organs at risk around the prostate; and 3)
establishing the relationship of pre- and post-treatment MRI to MRI-directed biopsy results
at 2-2.5 years after treatment.
- 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:
- NCT ID:
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.
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
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.
|LEAD RT||Active Comparator||LEAD: 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 RT||Active Comparator||HEIGHT: 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.|
- 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
- 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
- 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
- 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
- L. Ability to understand and the willingness to sign a written informed consent
- 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|
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|
|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|
|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|
|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|
|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|
|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|
|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|
|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).|
|Lead Sponsor:||University of Miami|
November 13, 2019