MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer (LEAD)
|ClinicalTrials.gov Identifier: NCT01411319|
Recruitment Status : Active, not recruiting
First Posted : August 8, 2011
Last Update Posted : November 17, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer Prostate Adenocarcinoma||Radiation: Lattice Extreme Ablative Dose Radiation Therapy Radiation: Standard IMRT Behavioral: EPIC SF-12 Questionnaire Behavioral: MAX-PC Questionnaire Behavioral: IPSS Questionnaire||Not Applicable|
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 dynamic contrast-enhanced MRI (DCE-MRI) and/or diffusion-weighted MRI (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 University of California Los Angeles (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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer|
|Actual Study Start Date :||December 27, 2011|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||May 2020|
Experimental: LEAD Radiation Therapy
Radiation: Lattice Extreme Ablative Dose Radiation Therapy
12 - 14 Gy dose pipes in 1 fraction to the multiparametric MRI defined gross tumor volumes (GTV) on Day 1.
Other Name: LEAD RT
Radiation: Standard IMRT
76 Gy in 38 fractions (2 Gy daily) of Standard Intensity-modulated radiation therapy (IMRT) starting on Day 2 for 7.5 weeks.
Other Name: IMRT
Behavioral: EPIC SF-12 Questionnaire
Expanded Prostate Cancer Index Composite-Short Form 12 (EPIC-SF12) quality of life questionnaire at various time points per study protocol.
Behavioral: MAX-PC Questionnaire
Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) quality of life questionnaire at various time points per study protocol.
Behavioral: IPSS Questionnaire
International Prostate Symptom Score (IPSS) quality of life questionnaire at various time points per study protocol.
- Proportion of Study Participants Experiencing Toxicity During Protocol Therapy [ Time Frame: From Day 1 to 30 Days Post-Completion of Protocol Therapy, About 12 Weeks ]The proportion of study participants experiencing Grade 2 or higher adverse events, serious adverse events and other toxicities 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: Up to 5.25 years ]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: 3 months, 9 months and up to 2.5 years Post-Completion of Protocol Therapy ]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).
- Quantification of Biomarker Expression in different prostate tumor regions [ Time Frame: Up to 2 to 2.5 years After Completion of Protocol Therapy ]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 at 2 to 2.5 years after completion of protocol therapy. [ Time Frame: 2 to 2.5 years After Completion of Protocol Therapy ]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.
- Rate of Failure-Free Survival [ Time Frame: Up to 5.25 years ]Rate of failure-free survival in study participants. Failure-free survival is defined as the elapsed time from study enrollment to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
- Rate of Overall Survival [ Time Frame: Up to 5.25 years ]Rate of Overall Survival in Study Participants. Overall Survival is defined as the elapsed time from study enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
- Assessment of Health-Related Quality of Life Using the EPIC SF-12 Questionnaire [ Time Frame: From Baseline to Post-Treatment, Up to 5.25 years ]Assessment of Health-Related Quality of Life (HRQOL) in the study participants using the Expanded Prostate Cancer Index Composite Questionnaire-SF12 (EPIC-SF12) at baseline, during last week of protocol therapy and at 6 weeks, 3 months, 9 months, 15 months, and then yearly to 5.25 years
- Assessment of Health-Related Quality of Life Using the MAX-PC Questionnaire [ Time Frame: From Baseline to Post-Treatment, Up to 5.25 years ]Assessment of Health-Related Quality of Life (HRQOL) in the study participants using the Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) baseline, during last week of protocol therapy and at 6 weeks, 3 months, 9 months, 15 months, and then yearly to 5.25 years
- Assessment of Health-Related Quality of Life Using the IPSS Questionnaire [ Time Frame: From Baseline to Post-Treatment, Up to 5.25 years ]Assessment of Health-Related Quality of Life (HRQOL) in the study participants using the International Prostate Symptom Score (IPSS) quality of life questionnaire at baseline, during last week of protocol therapy and at 6 weeks, 3 months, 9 months, 15 months, and then yearly to 5.25 years
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01411319
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Alan Pollack, MD. PhD||University of Miami|