A Phase I Trial of MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer (LEAD)
The hypotheses of this study are:
- Delivery of single fraction Lattice Extreme Ablative Dose (LEAD) radiotherapy (RT) to the dominant tumor lesion(s) in the prostate as identified by multiparametric functional Magnetic Resonance Imaging is safe and feasible.
- Biomarker expression levels differ in the functional MRI identified suspicious tumor regions and unsuspicious tumor regions. The investigators hypothesize that a significant source of variation in biomarker levels is due to tumor heterogeneity and that it is molecular abnormalities in the dominant tumor areas that are angiogenic and determine outcome.
Radiation: Lattice Extreme Ablative Dose (LEAD) Radiation Therapy
Radiation: Standard IMRT
Behavioral: EPIC SF-12 Questionnaire
Behavioral: MAX-PC Questionnaire
Behavioral: IPSS Questionnaire
Procedure: Blood Sample Collection
Procedure: Urine Sample Collection
Procedure: Prostate Biopsy
Procedure: CT Simulation
Procedure: MRI Simulation
Procedure: Fiducial Gold Marker Placement
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer|
- Number of Patients with Adverse Events in a Phase 1 LEAD RT Clinical Trial [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]To determine the number of patients with and severity of adverse events in a Phase 1 LEAD RT clinical trial.
- The proportion of enrolled patients for whom LEAD RT dose can be successfully administered following MRI-guided planning. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]The proportion of enrolled patients for whom LEAD RT dose can be successfully administered following MRI-guided planning.
- Measuring Risk of leaving tumor cells in prostate after LEAD RT [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]To measure the risk of leaving tumor cells in the prostate after LEAD RT by obtaining serial post-RT MRI's (3 months and 9 months, and within 2 months of the post-treatment prostate biopsy).
- Biomarker Expression in different prostate tumor regions [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]To quantify biomarker expression in different prostate tumor regions, comparing specifically the DCE-MRI enhancing and non-enhancing regions.
- Proportion of Study patients with positive prostate biopsies [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]To determine the proportion of study patients with positive prostate biopsies at 2-2.5 years after completion of therapy as a preliminary indication of the efficacy.
- Failure-free and Overall Progression [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]To report failure-free (biochemical and clinical progression) and overall survival.
- Assessment of Health-Related Quality of Life [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]To assess Health-Related Quality of Life (HRQOL) in the study patients.
|Study Start Date:||October 2010|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
|Experimental: LEAD Radiation Therapy||
Radiation: Lattice Extreme Ablative Dose (LEAD) Radiation Therapy
12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined GTV volumes on Day 1.
Other Name: LEAD RTRadiation: Standard IMRT
76 Gy in 38 fractions (2 Gy daily) of Standard IMRT starting on Day 2.
Other Name: IMRTBehavioral: EPIC SF-12 Questionnaire
Expanded Prostate Cancer Index Composite-SF12 (EPIC-SF12) quality of life questionnaire prior to radiation therapy, last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly thereafter up to 5.25 years.Behavioral: MAX-PC Questionnaire
Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) prior to radiation therapy, last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and yearly thereafter up to 5.25 years.Behavioral: IPSS Questionnaire
International Prostate Symptom Score (IPSS) prior to radiation therapy, last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months and every 6 months thereafter up to 5.25 years.Procedure: Blood Sample Collection
Plasma and Serum collection prior to radiation therapy, 24 hours post-LEAD RT, last week of radiation therapy, 6 weeks, 3 months, within 2 months of 2 year biopsyProcedure: Urine Sample Collection
Urine sample collection prior to radiation therapy, 24 hours post-LEAD RT, last week of radiation therapy, 6 weeks, 3 months, within 2 months of 2 year biopsyProcedure: Prostate Biopsy
Prostate biopsy prior to radiation therapy and 2 - 2.5 years post-completion of radiation therapy.Procedure: CT Simulation
Prior to radiation therapy.Procedure: MRI Simulation
Prior to radiation therapyProcedure: Fiducial Gold Marker Placement
Four (4) gold markers will be implanted in the prostate gland during prostate biopsy prior to radiation therapy.
The investigators propose to use a novel method for delivery of ablative spatially fractionated radiation to the multiparametric functional MRI defined tumor volume in the framework of a single-arm phase I clinical trial. The technique, deemed Lattice Extreme Ablative Dose (LEAD) RT, involves the creation of high doses shaped in cylinders through the DCE-MRI and/or DWI-MRI defined region(s) and adjacent apparently normal prostate in a lattice framework. The LEAD RT delivery will be in a single fraction of 12-14 Gy prior to standard fractions (2.0 Gy per day) for an additional 76 Gy (total dose for all treatments of 88-90 Gy and 149 Gy 3.0 in 2.0 Gy equivalents).
In this protocol the investigators also aim to examine biomarkers obtained from ultrasound-guided prostate biopsies. The patients will have the option of refusing the pre-RT prostate biopsies that are planned to be done when the patient has fiducial markers placed. Emphasis will be placed on biopsying regions in which the multiparametric MRI shows enhancement with or without DWI indicated water restriction. The preferred method of protocol research biopsies will involve the Eigen Artemis® system, which allows for fusion of the MRI images to ultrasound in real time. The Artemis® system is an FDA approved transrectal ultrasound prostate biopsy device. At the present time, Eigen has made available to us the MRI-ultrasound (MRIus) fusion software, which is in beta testing. The Eigen Artemis® system fusion software (not FDA approved) may be used to fine-tune the location of the tumor and biopsies by fusion of the previously obtained multiparametric MRI to the transrectal ultrasound in real time. The ultrasound is the true guidance imaging parameter that identifies the prostate boundaries and other nearby structures. The MRI is fused to the ultrasound such that the biopsies may be directed to a region in the ultrasound space.
The Eigen Artemis® system software will be used as a means of better targeting tumor regions, which are poorly seen on ultrasound alone. Recently, Natarajan et al (24) described the UCLA experience, demonstrating that the proportion of positive biopsies was much higher using the MRIus fusion software, as compared to ultrasound alone. In this protocol, the MRIus fusion software may be used to obtain research biopsies and the results of the biopsies (e.g., in terms of Gleason score) will not be used for diagnosis (the patients already have a diagnosis) or influence treatment in any way. The patient is free to withdraw from the protocol at any time, including upon learning the results of the biopsies.
If the Eigen Artemis system® is unavailable, ultrasound biopsies may be performed while viewing the functional MRI images on a separate monitor during the ultrasound-guided biopsies to enhance the probability of obtained biomarkers more representative of patient outcome. A third option that will become available in 2012 is to perform MRI-guided biopsies directly on the MRI scanner using a commercially available approach.. Biomarkers from biopsies from the index lesion(s) will be compared to those from tumor in other areas of the prostate. Biopsy tissues will be collected pre- and post-treatment and analyzed by immunohistochemistry (IHC) for biomarker quantification.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01411319
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Alan Pollack, MD. PhD||University of Miami|