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

This study is currently recruiting participants.
Verified February 2014 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: February 28, 2014
Last verified: February 2014

August 3, 2011
February 28, 2014
May 2011
May 2017   (final data collection date for primary outcome measure)
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).
Same as current
Complete list of historical versions of study NCT01411332 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
  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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prostate Cancer
  • Prostate Adenocarcinoma
  • 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).
  • 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
  • Active Comparator: Arm I: SIMRT
    Arm I: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
    Interventions:
    • Radiation: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT)
    • 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
  • Active Comparator: Arm II: HTIMRT
    Arm II: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT)
    Interventions:
    • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
May 2017
May 2017   (final data collection date for primary outcome measure)

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.
Male
35 Years to 85 Years
No
Not Provided
United States
 
NCT01411332
UMIAMI-20100635
Yes
University of Miami Sylvester Comprehensive Cancer Center
University of Miami Sylvester Comprehensive Cancer Center
Not Provided
Principal Investigator: Alan Pollack, MD, PhD University of Miami Sylvester Comprehensive Cancer Center
University of Miami Sylvester Comprehensive Cancer Center
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP