A Phase I Trial of MRI-Guided Lattice Extreme Ablative Dose Radiotherapy For Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
University of Miami
ClinicalTrials.gov Identifier:
NCT01411319
First received: August 3, 2011
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

The hypotheses of this study are:

  1. 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.
  2. 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 Intervention Phase
Prostate Cancer
Prostate Adenocarcinoma
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
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 20
Study Start Date: October 2010
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LEAD Radiation Therapy Radiation: Lattice Extreme Ablative Dose (LEAD) Radiation Therapy
12 - 14 Gy dose pipes in 1 fraction to multiparametric MRI on Day 1.
Other Name: LEAD RT
Radiation: Standard IMRT
76 Gy in 38 fractions (2 Gy daily) of Standard IMRT starting on Day 2.
Other Name: IMRT
Behavioral: 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 biopsy
Procedure: 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 biopsy
Procedure: 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 therapy
Procedure: Fiducial Gold Marker Placement
Four (4) gold markers will be implanted in the prostate gland during prostate biopsy prior to radiation therapy.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Biopsy confirmed adenocarcinoma of the prostate.
  • T1-T2 disease based on digital rectal exam (DRE).

    • T3a disease based on MRI only (not DRE) is acceptable.
  • Gleason score 6-10.
  • Patients with Gleason score 8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 months (short term ADT) is permitted (not required) on this protocol. The ADT is recommended to begin after fiducial marker placement; however, ADT is permitted to have been started up to two months prior to the signing of consent. All patients in this protocol may (not required) be treated with 4-6 months of ADT, at the discretion of the treating physician.

    • Gleason >= 8 must have < 40% of the tissue involved with Gleason 8 in the biopsy specimen.
  • PSA =< 30 ng/mL within 3 months of enrollment. If PSA was above 20 and dropped to =< 20 with antibiotics, this is acceptable for enrollment.
  • No previous pelvic radiotherapy.
  • No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable).
  • 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.
  • Identifiable multiparametric-MRI tumor lesion or lesions, that total in volume < 33% of the prostate

    • Multiparametric MRI of prostate and pelvis is required prior to protocol consideration.
    • If contrast not given, the point dose on the ADC map should be < 1000.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Zubrod performance status < 2.
  • Willingness to fill out quality of life forms.
  • Bone scan negative if PSA > 15 ng/mL or Gleason >= 8 disease. A questionable bone scan is acceptable if other imaging tests are negative for metastasis.
  • Serum testosterone is within 40% of normal assay limits (e.g., x=0.4*lower assay limit and x=.04*upper assay limit + upper assay limit), and taken within 4 months of enrollment. Patients who have been started on ADT prior to signing consent are not required to have a serum testosterone at this level prior to signing consent; but, a serum testosterone prior to fiducial marker placement is recommended.
  • Serum liver function tests (LFT) are within 40% of normal assay limits and taken within 3 months of enrollment.
  • Complete blood counts are within 40% of normal assay limits, taken within 3 months of enrollment.
  • Age >= 35 and =< 85 years.

Exclusion Criteria:

  • > T3a disease on digital rectal exam or >T3a disease clearly identified by MRI.
  • Gleason score < 6 and > 8.
  • >= 40% Gleason 8-10 tumor, over the total tissue including other tumor and normal tissue. For example: (Gleason 8-10 tumor length/other biopsy tissue length)*100 = >= 40%.
  • Patients are not eligible if they have been started on androgen deprivation therapy prior to enrollment.
  • Androgen deprivation therapy longer than 6 months. Androgen deprivation timing is for the Luteinizing hormone-releasing hormone (LHRH) agonist portion only and not when anti-androgen is started beforehand with the purpose of counteracting the surge in testosterone from the LHRH agonist
  • PSA > 30 ng/mL within 3 months of enrollment.
  • Unable to obtain a 1.5T or 3.0T multiparametric MRI of the pelvis and prostate with contrast.
  • Unidentifiable multiparametric MRI tumor lesion.
  • Identifiable multiparametric-MRI tumor lesions, that total in volume >= 33% of the prostate.
  • Previous pelvic radiotherapy.
  • Previous history of radical prostatectomy.
  • Concurrent, active malignancy, which is not 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 not eligible.
  • Zubrod performance status >= 2.
  • Inability to understand or unwilling to sign a written informed consent document
  • Unwilling to fill out quality of life/psychosocial forms.
  • Bone scan is positive and other imaging tests confirm a suspicion of metastasis from prostate cancer.
  • Serum testosterone is not within 40% of normal assay limits taken within 4 months of enrollment (only applicable to patients not started on ADT prior to signing consent).
  • Serum liver function tests (LFTs) are not within 40% of normal assay limits taken within 3 months of enrollment.
  • Complete blood counts are not within 40% of normal assay limits taken within 3 months of enrollment.
  • Age < 35 and > 85 years.
  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: NCT01411319

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Alan Pollack, MD    866-574-5124    apollack@med.miami.edu   
Sub-Investigator: Brian Lally, MD         
Sub-Investigator: Arnold Markoe, MD         
Principal Investigator: Alan Pollack, MD, PhD         
Sub-Investigator: Lorraine Portelance, MD         
Sub-Investigator: Cristiane Takita, MD         
Sub-Investigator: Aaron Wolfson, MD         
Sub-Investigator: Jean Wright, MD         
Sub-Investigator: Charles Lync, MD         
Sub-Investigator: Bruce Kava, MD         
Sub-Investigator: Radka Stoyanova, PhD         
Sub-Investigator: Javier Casillas, MD         
Sub-Investigator: Mehrdad Nadji, MD         
Sub-Investigator: Saleem Umar, MD         
Sub-Investigator: Xiaodong Wu, PhD         
Sub-Investigator: Mansoor Ahmed, MD         
Sub-Investigator: Frank Penedo, PhD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Alan Pollack, MD. PhD University of Miami
  More Information

No publications provided

Responsible Party: University of Miami
ClinicalTrials.gov Identifier: NCT01411319     History of Changes
Other Study ID Numbers: UMIAMI-20100389
Study First Received: August 3, 2011
Last Updated: February 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
Prostate Cancer
Prostate Adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on July 24, 2014