Radiation Hypofractionation Via Extended Versus Accelerated Therapy (HEAT) For Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Matthew Abramowitz, University of Miami
ClinicalTrials.gov Identifier:
NCT01794403
First received: February 14, 2013
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

Accelerated Hypofractionation Radiotherapy for prostate cancer of 36.25 Gy delivered in 5 fractions will not be inferior to the standard treatment of 70.2 Gy given in 26 fractions with respect to two-year failure defined as a positive biopsy two years post treatment completion or earlier evidence of biochemical or clinical failure.


Condition Intervention Phase
Prostate Cancer
Radiation: Extended Hypofractionation Radiotherapy
Radiation: Accelerated Hypofractionation Radiotherapy
Procedure: Fiducial Marker Placement
Behavioral: Quality of Life Questionnaires
Procedure: Prostate Biopsy
Genetic: Biopsy Tissue for Biomarkers
Genetic: Biofluids for proteomics and genomics studies
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study of Radiation Hypofractionation Via Extended Versus Accelerated Therapy (HEAT) For Prostate Cancer

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Compare the two-year failure rates (biochemical or clinical failure, or positive biopsy) between the treatment arms (AHRT and EHRT) using a noninferiority margin of 12%. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare acute toxicity rates of AHRT and EHRT. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Compare Efficacy of AHRT with EHRT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Compare the efficacy of AHRT with EHRT for the treatment of low and early intermediate risk prostate cancer, where efficacy is defined by biochemical failure using Phoenix (Nadir+2) definition or clinical failure.

  • Compare AHRT and EHRT overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Compare AHRT and EHRT with respect to prostate cancer mortality and overall survival.

  • Compare AHRT and EHRT quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Compare AHRT and EHRT with respect to quality of life (QOL), including erectile dysfunction rates, in generic and organ-specific domains.

  • Rates of ASTRO-defined biochemical failure. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Relationship of biomarkers from pretreatment diagnostic tissue and blood to the efficacy endpoints, toxicity and QOL. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Examine the relationship of biomarkers from pretreatment diagnostic tissue and blood to the efficacy endpoints, toxicity and QOL.

  • Rates of late-occurring grade 2 or greater GI/GU toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To compare the rates of late-occurring grade 2 or greater G.I. or GU toxicity.

  • Effectiveness of AHRT and EHRT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate the comparative effectiveness of each treatment regimen.

  • Cost utility of AHRT and EHRT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Examine the cost utility of each treatment regimen.


Estimated Enrollment: 75
Study Start Date: March 2013
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Extended Hypofractionation Radiotherapy (EHRT)
A total dose of 70.2 Gy will be delivered in 26 fractions, 2.7 Gy to the Planning Target Volume (PTV) by Intensity Modulated Radiotherapy (IMRT) with stationary gantry or rotating gantry technique.
Radiation: Extended Hypofractionation Radiotherapy
A total dose of 70.2 Gy will be delivered in 26 fractions, 2.7 Gy to the Planning Target Volume (PTV) by Intensity Modulated Radiotherapy (IMRT) with stationary gantry or rotating gantry technique.
Other Name: EHRT
Procedure: Fiducial Marker Placement
All patients will have 3-4 gold fiducial seeds or tracking markers placed in the prostate under ultrasound guidance (biopsy) prior to treatment planning by MRI and/or CT.
Behavioral: Quality of Life Questionnaires

The Expanded Prostate Cancer Index Composite Questionnaire-SF-12 (EPIC-SF-12) at after enrollment, prior to radiation therapy, and post-therapy at 6 weeks, 3 months, 9 months, 15 months, and then yearly to 5.25 years.

Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) at after enrollment, prior to radiation therapy, and post-therapy at at 6 weeks, 3 months, 9 months, 15 months and then yearly to 5.25 years.

International Prostate Symptom Index (IPSS) after enrollment, prior to radiation therapy, last week of therapy, and post-therapy at at 6 weeks, 3 months, and then every 6 months for 5.25 years.

Other Names:
  • The Expanded Prostate Cancer Index Composite SF-12 Questionnaire
  • EPIC-SF-12
  • Memorial Anxiety Scale for Prostate Cancer patients
  • MAX-PC
  • International Prostate Symptom Score
  • IPSS
Procedure: Prostate Biopsy
Prostate biopsy at 2 - 2.5 years post completion of all therapy. Additional as needed.
Other Name: Prostate Biopsy
Genetic: Biopsy Tissue for Biomarkers
Biomarker analysis of the DNA content (image analysis) and immunohistochemical analyses of Ki-67/MIB-1, p53, bcl-2, bax, MDM2, and PKA in biopsy tissue.
Genetic: Biofluids for proteomics and genomics studies
Blood and urine samples. Four tubes of approximately 10 cc of blood each will be collected prior to treatment. Approximately 50 mL of urine will be collected.
Active Comparator: Accelerated Hypofractionation Radiotherapy (AHRT)
A total dose of 36.25 Gy will be delivered in 5 fractions, 7.25 Gy each to the Planning Target Volume (PTV), by Stereotactic Body Radiotherapy (SBRT) techniques.
Radiation: Accelerated Hypofractionation Radiotherapy
A total dose of 36.25 Gy will be delivered in 5 fractions, 7.25 Gy each to the Planning Target Volume (PTV), by Stereotactic Body Radiotherapy (SBRT) techniques.
Other Name: AHRT
Procedure: Fiducial Marker Placement
All patients will have 3-4 gold fiducial seeds or tracking markers placed in the prostate under ultrasound guidance (biopsy) prior to treatment planning by MRI and/or CT.
Behavioral: Quality of Life Questionnaires

The Expanded Prostate Cancer Index Composite Questionnaire-SF-12 (EPIC-SF-12) at after enrollment, prior to radiation therapy, and post-therapy at 6 weeks, 3 months, 9 months, 15 months, and then yearly to 5.25 years.

Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) at after enrollment, prior to radiation therapy, and post-therapy at at 6 weeks, 3 months, 9 months, 15 months and then yearly to 5.25 years.

International Prostate Symptom Index (IPSS) after enrollment, prior to radiation therapy, last week of therapy, and post-therapy at at 6 weeks, 3 months, and then every 6 months for 5.25 years.

Other Names:
  • The Expanded Prostate Cancer Index Composite SF-12 Questionnaire
  • EPIC-SF-12
  • Memorial Anxiety Scale for Prostate Cancer patients
  • MAX-PC
  • International Prostate Symptom Score
  • IPSS
Procedure: Prostate Biopsy
Prostate biopsy at 2 - 2.5 years post completion of all therapy. Additional as needed.
Other Name: Prostate Biopsy
Genetic: Biopsy Tissue for Biomarkers
Biomarker analysis of the DNA content (image analysis) and immunohistochemical analyses of Ki-67/MIB-1, p53, bcl-2, bax, MDM2, and PKA in biopsy tissue.
Genetic: Biofluids for proteomics and genomics studies
Blood and urine samples. Four tubes of approximately 10 cc of blood each will be collected prior to treatment. Approximately 50 mL of urine will be collected.

  Eligibility

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

Inclusion Criteria:

  • Histologically proven prostate adenocarcinoma.

    • Gleason score 2-7 (reviewed by reference lab at UM).
    • Biopsy within one year of date of enrollment.
  • Clinical stage ≤ T2 based on DRE and/or ≤ T3a based on MRI (if done); N0-Nx; M0-Mx (AJCC 7th Edition)

    • T-stage and N-stage determined by physical exam and available imaging studies (CT, and/or MRI of the pelvis; see section 4.5). For MRI, questionable extracapsular extension is permitted. To distinguish blood from tumor the ideal study would be to acquire T2, T1 noncontrast and T1 dynamic contrast enhanced sequence, although this is not required. A small amount of extracapsular extension is permitted, as long as it can be included in the CTV and the constraints are met.
    • M-stage determined by physical exam, CT or MRI. Bone scan not required unless clinical findings suggest possible osseous metastases.
  • PSA ≤ 15 ng/ml, obtained no greater than 3 months prior to enrollment.
  • Patients belonging in one of the following risk groups:

    • Low:

      • Clinical stage* T1-T2; Gleason ≤ 6, PSA ≤ 10 & <50% biopsy cores positive.
    • Intermediate:

      • Clinical stage T2b-T2c; Gleason ≤ 6, PSA ≤ 10 & <50% biopsy cores positive.
      • Clinical stage T1-T2; Gleason ≤ 6, PSA ≤ 10 & ≥50% biopsy cores positive.
      • Clinical stage T1-T2; Gleason = 7, PSA ≤ 10 & <50% biopsy cores positive or T1-T2; Gleason ≤ 6 & PSA >10 and ≤15 & <50% biopsy cores positive.
      • MRI stage T3a with evidence of extraprostatic extension is allowed.
    • Clinical stage is based on digital rectal exam (DRE). Seminal vesicle invasion on MRI is not eligible. T1a should be permitted if subsequent peripheral zone biopsies show tumor.
  • Prostate volume: ≤ 80 cc.

    • Determined using: volume = π/6 x length x height x width.
    • Measured from CT or MRI ≤90 days prior to enrollment.
  • Zubrod performance status 0-1.
  • No prior total prostatectomy or cryotherapy of the prostate.

    • Prior suprapubic prostatectomy, transurethral resection and laser ablation are permitted.
  • No prior radiotherapy to the prostate or lower pelvis.
  • No implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery, in the investigator's opinion.
  • No chemotherapy for a malignancy in the last 5 years.
  • No history of an invasive malignancy (other than this prostate cancer, or nonmetastatic basal or squamous skin cancers) in the last 5 years.
  • No more than 4 months of androgen deprivation therapy (ADT) prior to enrollment. If given, prior to enrollment, ADT cannot be continued during radiation or plan to delivered after the completion of radiation therapy.
  • Patient must be able to have gold fiducial markers placed in the prostate (if on anticoagulants, must be cleared by a primary care physician or cardiologist), or if patient already has fiducial marker placed, they must be in accordance with the protocol specifications (Section 4.2.2)
  • Ability to understand and the willingness to sign a written informed consent document.
  • Willingness to fill out quality of life/psychosocial forms.
  • Age >= 35 and =< 85 years.
  • IPSS (AUA) score ≤12

Exclusion Criteria:

  • Does not have a diagnosis of prostate adenocarcinoma.
  • Patient has clinical T3a or any evidence of T3b disease.
  • Patient has stage N1 or M1 disease.
  • Patients has a PSA of greater than 15 ng/ml.
  • Patient does not meet any of the risk groups outlined in section 3.1.4.
  • Prostate volume greater than 80 cc.
  • Zubrod performance status 2 or greater.
  • Prior total prostatectomy.
  • Prior radiation therapy to the prostate or lower pelvis.
  • Implanted hardware which limits treatment planning or delivery (determined by the investigator).
  • Chemotherapy within the past 5 years.
  • Diagnosis of an invasive malignancy within 5 years (other than current prostate cancer or non-metastatic basal or squamous skin cancers).
  • The use of more than 4 months of androgen deprivation therapy (ADT) prior to enrollment, or plans for ADT to be continued during radiation to be delivered after the completion of radiation therapy.
  • Inability to have gold fiducial markers placed in the prostate, or fiducial markers already placed that are not in accordance with the protocol (Section 4.2.2)
  • Unwilling or inability to give informed consent.
  • Not willing to fill out quality of life/psychosocial questionnaires.
  • IPSS score > to 12.
  • 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: NCT01794403

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Matthew C Abramowitz, MD    305-243-4200    mabramowitz@med.miami.edu   
Contact: University of Miami Sylvester Comprehensive Cancer Center    866-574-5124    sylvester@emergingmed.com   
Principal Investigator: Matthew Abramowitz, MD         
Sub-Investigator: Saleem Umar, MD         
Sub-Investigator: Radka Stoyanova, PhD         
Sub-Investigator: Javier Casillas, MD         
Sub-Investigator: Charles Lynne, MD         
Sub-Investigator: Margaret Byrne, PhD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Matthew Abramowitz, MD University of Miami
Principal Investigator: Alan Pollack, MD, PhD University of Miami
  More Information

No publications provided

Responsible Party: Matthew Abramowitz, Assistant Professor of Clinical, University of Miami
ClinicalTrials.gov Identifier: NCT01794403     History of Changes
Other Study ID Numbers: 20110491
Study First Received: February 14, 2013
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Prostate Cancer
Prostate
Radiation Therapy
Hypofractionation Radiotherapy
Extended Hypofractionation Radiotherapy
Accelerated Hypofractionation Radiotherapy
AHRT
EHRT

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on September 14, 2014