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A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial

This study is currently recruiting participants.
Verified April 2013 by University of Miami Sylvester Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01411332
First received: August 3, 2011
Last updated: April 18, 2013
Last verified: April 2013
History of Changes
  Purpose
  1. Delivery of directed hypofractionated targeted (HT) radiotherapy (RT) tumor boost to the dominant tumor lesion in the prostate as identified by Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) will increase tumor eradication from the prostate.
  2. Biomarker expression levels differ in the DCE-MRI enhancing and non-enhancing tumor regions.
  3. 10-15% of men undergoing RT have Circulating DNA or tumor cells (CTC) that are related to an adverse treatment outcome.
  4. Quality of life will not differ significantly between the treatment arms.
  5. Prostate cancer-related anxiety will be reduced in the HTIMRT arm, because the patients will be aware that the dominant tumor will be targeted with higher radiation dose.

Condition Intervention Phase
Prostate Cancer
Prostate Adenocarcinoma
 Radiation: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
Radiation: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
Behavioral: EPIC SF-12 Questionnaire
Behavioral: MAX-PC Questionnaire
Behavioral: IPSS Questionnaire
Procedure: Ultra-Sound Guided Biopsy
Procedure: Prostate Fiducial Marker Placement
Procedure: Blood Sample Collection
Procedure: DCE-MRI
Procedure: CT Simulation
Procedure: MRI Simulation
Procedure: Bone Scan
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • To compare the rate of prostate biopsy positivity after HTIMRT to SIMRT at 2 years after all therapy. [ Time Frame: 2 - 2.5 years post-therapy ] [ Designated as safety issue: No ]
    The proportion of positive biopsy findings among patients without clinical or biochemical failure 2-2.5 years after completing study treatment (RT or ADT, whichever is longer).


Secondary Outcome Measures:
  • Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial. [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]
    Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial.

  • To evaluate the influence of HTIMRT to health-related quality of life (HRQOL), prostate cancer-specific anxiety and prostate cancer-specific QOL. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Two contemporary instruments (questionnaires) will be utilized to assess patient function and bother (Expanded Prostate Cancer Index Composite-SF12 (EPIC-SF12) and the prostate cancer-specific anxiety Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC).

  • To quantify biomarker expression in different prostate tumor regions, comparing specifically the DCE-MRI enhancing and non-enhancing regions. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.

  • To evaluate the incidence and relationship of circulating free DNA and tumor cells to tissue biomarkers and prostate biopsy positivity at 2 years after completion of therapy. [ Time Frame: 2 years post-completion of therapy ] [ Designated as safety issue: No ]
    The investigators test whether absolute pretreatment CTC counts and treatment-induced changes in CTC counts as assessed on our novel microfilter platform correlate with response to therapy (biopsy positivity at two years after treatment).

  • Biochemical failure or clinical failure [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at TURP. Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.

  • Failure-free Survival (FFS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The elapsed time from start of radiotherapy 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.

  • Overall Survival (OS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.


Estimated Enrollment: 72
Study Start Date: May 2011
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I: SIMRT
Arm I: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
 Radiation: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
A total dose of 80 Gy will be delivered in 40 fractions to the Clinical Target Volume (CTV).
Behavioral: EPIC SF-12 Questionnaire
Expanded Prostate Cancer Index Composite-SF12 (EPICSF-SF12) quality of life questionnaire prior to radiation therapy, during the last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months, and yearly up to 5.25 years after radiation therapy.
Behavioral: MAX-PC Questionnaire
Expanded Prostate Cancer Index Composite-SF12 (EPICSF-SF12) quality of life questionnaire prior to radiation therapy, during the last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months, and yearly up to 5.25 years after radiation therapy.
Behavioral: IPSS Questionnaire
International Prostate Symptom Score (IPSS) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months and every 6 months up to 5.25 years post-radiation therapy.
Procedure: Ultra-Sound Guided Biopsy
Ultra-Sound Guided Biopsy prior to radiation therapy and 2 - 2.5 years post-completion of radiation therapy.
Procedure: Prostate Fiducial Marker Placement
Prostate Fiducial Marker implanted in prostate tissue during Ultrasound Guided Biopsy prior to radiation therapy, within 4 weeks after enrollment.
Procedure: Blood Sample Collection
Plasma and serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months post-radiation therapy and within 2 months of 2 year Ultrasound-Guided prostate biopsy.
Procedure: DCE-MRI
Dynamic Contrast Enhanced MRI of Pelvis/Prostate prior to radiation therapy. 3 months post-completion of radiation therapy, and within 2 months of 2 year Ultrasound guided prostate biopsy
Procedure: CT Simulation
CT Simulation prior to radiation therapy.
Procedure: MRI Simulation
MRI Simulation prior to radiation therapy.
Procedure: Bone Scan
Bone Scan as needed
Active Comparator: Arm II: HTIMRT
Arm II: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
 Radiation: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
Dose escalation to the Dynamic Contrast Enhanced MRI (DCE-MRI)-defined dominant region(s) by dose painting at 2.35 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 76 Gy. The hypofractionated targeted (HT) boost region will receive an absolute dose of 89.3 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 95.5 Gy in 2.0 Gy fractions.
Behavioral: EPIC SF-12 Questionnaire
Expanded Prostate Cancer Index Composite-SF12 (EPICSF-SF12) quality of life questionnaire prior to radiation therapy, during the last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months, and yearly up to 5.25 years after radiation therapy.
Behavioral: MAX-PC Questionnaire
Expanded Prostate Cancer Index Composite-SF12 (EPICSF-SF12) quality of life questionnaire prior to radiation therapy, during the last week of radiation therapy, 6 weeks, 3 months, 9 months, 15 months, and yearly up to 5.25 years after radiation therapy.
Behavioral: IPSS Questionnaire
International Prostate Symptom Score (IPSS) questionnaire prior to radiation therapy, during last week of radiation therapy, 6 weeks, 3 months and every 6 months up to 5.25 years post-radiation therapy.
Procedure: Ultra-Sound Guided Biopsy
Ultra-Sound Guided Biopsy prior to radiation therapy and 2 - 2.5 years post-completion of radiation therapy.
Procedure: Prostate Fiducial Marker Placement
Prostate Fiducial Marker implanted in prostate tissue during Ultrasound Guided Biopsy prior to radiation therapy, within 4 weeks after enrollment.
Procedure: Blood Sample Collection
Plasma and serum sample collection prior to radiation therapy, during last week of radiation therapy, 3 months post-radiation therapy and within 2 months of 2 year Ultrasound-Guided prostate biopsy.
Procedure: DCE-MRI
Dynamic Contrast Enhanced MRI of Pelvis/Prostate prior to radiation therapy. 3 months post-completion of radiation therapy, and within 2 months of 2 year Ultrasound guided prostate biopsy
Procedure: CT Simulation
CT Simulation prior to radiation therapy.
Procedure: MRI Simulation
MRI Simulation prior to radiation therapy.
Procedure: Bone Scan
Bone Scan as needed

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy confirmed adenocarcinoma of the prostate.

  • T1-T2 disease based on digital rectal exam.

    • T1a is permitted if peripheral zone biopsies are positive.
    • T3a disease based on MRI only is acceptable.
  • No evidence of metastasis by any clinical criteria or available radiographic tests.
  • Gleason score 6-8.

  • 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 on this protocol. Gleason score 8 patients should be recommended to receive short term ADT in conjunction with RT. When given, the ADT should begin after fiducial marker placement.

    • Patients with Gleason score 8 disease must have <20% of the diagnostic tumor tissue involved with tumor.
    • Patients with Gleason score ≤7 may be treated with 4-6 months of ADT if ≥20% of the biopsy tissue is, or ≥50% of the cores are, positive for tumor.
  • PSA ≤20 ng/mL within 8 weeks of enrollment.
  • Bone scan negative if PSA ≥10 ng/mL or Gleason 8 disease.
  • If PSA is >10 ng/ml or there is Gleason 8 disease, a bone scan should be obtained ≤4 months before enrollment and should be without evidence of metastasis. A questionable bone scan is acceptable if plain x-rays and/or MRI are negative for metastasis.
  • 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 DCE-MRI tumor lesion or lesions, that total in volume <33% of the prostate within 8 weeks prior to protocol entry.

    • DCE-MRI of prostate and pelvis is required prior to protocol consideration
  • Ability to understand and the willingness to sign a written informed consent document
  • Zubrod performance status <2
  • Willingness to fill out quality of life/psychosocial forms.
  • Age ≥35 and ≤85 years.
  • Serum testosterone is within 40% of normal assay limits, taken within 4 months of enrollment.
  • Serum LFTs are within 40% of normal assay limits, taken within 8 weeks of enrollment.
  • Complete blood counts are within 40% of normal assay limits, taken within 8 weeks of enrollment.
  • BUN and creatinine are within 40% of normal assay limits, taken within 8 weeks of enrollment.

Exclusion Criteria:

  • >T2 on digital rectal exam.
  • >T3a (T3b/T4) disease identified by MRI.
  • Gleason score <6 or >8.
  • Gleason score 8 disease and ≥20% of the diagnostic tissue containing tumor. For example: (tumor length/other biopsy tissue length)*100 = ≥20%.
  • Patients are not eligible if they have been started on androgen deprivation therapy prior to enrollment.
  • Androgen deprivation therapy planned for 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.
  • PSA >20 ng/mL within 8 weeks of enrollment.
  • Unable to obtain a 3T MRI of the pelvis and prostate with contrast prior to enrollment.
  • Unidentifiable distinct DCE-MRI tumor lesion.
  • Identifiable DCE-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.
  • Not willing to fill out quality of life/psychosocial questionnaires.
  • Age <35 and >85 years.
  • Serum testosterone is < 40% of normal assay limits, taken within within 4 months of enrollment.
  • Serum LFTs are < 40% of normal assay limits, taken within within 8 weeks of enrollment.
  • Complete blood counts are < 40% of normal assay limits, taken within within 8 weeks of enrollment.
  • BUN and creatinine are <40% of normal assay limits, taken within 8 weeks of enrollment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01411332

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Alan Pollack, MD, PhD     305-243-4916     apollack@med.miami.edu    
Contact: University of Miami Sylvester Comprehensive Cancer Center     866-574-5124     Sylvester@emergingmed.com    
Sub-Investigator: Matthew Abramowitz, MD            
Sub-Investigator: Brian Lally, MD            
Sub-Investigator: Arnold Markoe, MD            
Sub-Investigator: Lorraine Portelance, MD            
Sub-Investigator: Cristiane Takita, MD            
Sub-Investigator: Aaron Wolfson, MD            
Sub-Investigator: Jean Wright, MD            
Sub-Investigator: Charles Lynn, MD            
Sub-Investigator: Bruce Kava, MD            
Sub-Investigator: Rakesh Singal, MD            
Sub-Investigator: Radka Stoyanova, MD            
Sub-Investigator: Javier Casillas, MD            
Sub-Investigator: Mehrdad Nadji, MD            
Sub-Investigator: Saleem Umar, MD            
Sub-Investigator: Xiaodong Wu, PhD            
Sub-Investigator: Bal Lokeshwar, PhD            
Sub-Investigator: Ram Datar, PhD            
Sub-Investigator: Jennifer Hu, PhD            
Sub-Investigator: Frank Penedo, PhD            
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Principal Investigator: Alan Pollack, MD, PhD University of Miami Sylvester Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01411332     History of Changes
Other Study ID Numbers: EPROST-20100635
Study First Received: August 3, 2011
Last Updated: April 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
Prostate Cancer
Prostate Adenocarcinoma

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

ClinicalTrials.gov processed this record on May 19, 2013