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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01794403




Registration number
NCT01794403
Ethics application status
Date submitted
14/02/2013
Date registered
18/02/2013
Date last updated
22/06/2020

Titles & IDs
Public title
Radiation Hypofractionation Via Extended Versus Accelerated Therapy (HEAT) For Prostate Cancer
Scientific title
A Randomized Study of Radiation Hypofractionation Via Extended Versus Accelerated Therapy (HEAT) For Prostate Cancer
Secondary ID [1] 0 0
20110491
Universal Trial Number (UTN)
Trial acronym
HEAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Extended Hypofractionation Radiotherapy
Treatment: Other - Accelerated Hypofractionation Radiotherapy
Behaviour - Expanded Prostate Cancer Index Composite SF-12
Behaviour - International Prostate Symptom Score
Behaviour - Memorial Anxiety Scale for Prostate Cancer patients

Active Comparator: Extended Hypofractionation (EHRT) - Extended Hypofractionation Radiotherapy: A total dose of 70.2 Gy, 26 fractions, 2.7 Gy to the Planning Target Volume (PTV).
Expanded Prostate Cancer Index Composite SF-12 (EPIC SF-12) quality of life questionnaire;
International Prostate Symptom Score (IPSS) quality of life questionnaire;
Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) quality of life questionnaire;
OPTIONAL: Ultrasound-guided biopsy, blood and urine samples for correlative studies.

Experimental: Accelerated Hypofractionation (AHRT) - Accelerated Hypofractionation Radiotherapy: A total dose of 36.25 Gy, 5 fractions, 7.25 Gy each to the Planning Target Volume (PTV);
Expanded Prostate Cancer Index Composite SF-12 (EPIC SF-12) quality of life questionnaire;
International Prostate Symptom Score (IPSS) quality of life questionnaire;
Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) quality of life questionnaire;
OPTIONAL: Ultrasound-guided biopsy, blood and urine samples for correlative studies.


Treatment: Other: 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.

Treatment: Other: 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.

Behaviour: Expanded Prostate Cancer Index Composite SF-12
The Expanded Prostate Cancer Index Composite SF-12 (EPIC-SF-12) quality of life questionnaire to be administered to study participants at protocol-defined intervals.

Behaviour: International Prostate Symptom Score
International Prostate Symptom Score quality of life questionnaire to be administered to study participants at protocol-defined intervals.

Behaviour: Memorial Anxiety Scale for Prostate Cancer patients
Memorial Anxiety Scale for Prostate Cancer patients quality of life questionnaire to be administered to study participants at protocol-defined intervals.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Behaviour
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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%.
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Compare acute toxicity rates of AHRT and EHRT.
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Compare Efficacy of AHRT with EHRT - 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.
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Compare AHRT and EHRT overall survival - Compare AHRT and EHRT with respect to prostate cancer mortality and overall survival.
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Compare AHRT and EHRT quality of life - Compare AHRT and EHRT with respect to quality of life (QOL), including erectile dysfunction rates, in generic and organ-specific domains.
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Rates of ASTRO-defined biochemical failure.
Timepoint [5] 0 0
2 years
Secondary outcome [6] 0 0
Relationship of biomarkers from pretreatment diagnostic tissue and blood to the efficacy endpoints, toxicity and QOL. - Examine the relationship of biomarkers from pretreatment diagnostic tissue and blood to the efficacy endpoints, toxicity and QOL.
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Rates of late-occurring grade 2 or greater GI/GU toxicity - To compare the rates of late-occurring grade 2 or greater gastrointestinal (GI) or genitourinary (GU) toxicity.
Timepoint [7] 0 0
2 years
Secondary outcome [8] 0 0
Effectiveness of AHRT and EHRT - Evaluate the comparative effectiveness of each treatment regimen.
Timepoint [8] 0 0
2 years
Secondary outcome [9] 0 0
Cost utility of AHRT and EHRT - Examine the cost utility of each treatment regimen.
Timepoint [9] 0 0
2 years

Eligibility
Key inclusion criteria
1. Histologically proven prostate adenocarcinoma.

- Gleason score 2-7 (reviewed by reference lab at UM).

- Biopsy within one year of date of enrollment.

2. 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 clinical target
volume (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.

3. Prostate-Specific Antigen (PSA) < 20 ng/ml, obtained no greater than 3 months prior to
enrollment.

4. 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 < 20 & < 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.

5. Prostate volume: = 80 cc.

- Determined using: volume = p/6 x length x height x width.

- Measured from CT or MRI =90 days prior to enrollment.

6. Zubrod performance status 0-1.

7. No prior total prostatectomy or cryotherapy of the prostate.

- Prior suprapubic prostatectomy, transurethral resection and laser ablation are
permitted.

8. No prior radiotherapy to the prostate or lower pelvis.

9. No implanted hardware or other material that would prohibit appropriate treatment
planning or treatment delivery, in the investigator's opinion.

10. No chemotherapy for a malignancy in the last 5 years.

11. No history of an invasive malignancy (other than this prostate cancer, or
nonmetastatic basal or squamous skin cancers) in the last 5 years.

12. 4-6 months of androgen deprivation therapy (ADT) are allowed for intermediate risk
patients. This must be declared prior to randomization. This may not have been started
more than 2 months prior to randomization.

13. 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). NOTE: If a method of intrafraction prostate
tracking is available which does not require fiducial markers, this will be adequate
for this trial (i.e. 4D transperitoneal ultrasound, onboard MRI guidance).

14. Ability to understand and the willingness to sign a written informed consent document.

15. Willingness to fill out quality of life/psychosocial forms.

16. Age >= 35 and =< 85 years.

17. IPSS (AUA) score =12
Minimum age
35 Years
Maximum age
85 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Does not have a diagnosis of prostate adenocarcinoma.

2. Patient has clinical T3a or any evidence of T3b disease.

3. Patient has stage N1 or M1 disease.

4. Patients has a PSA of greater than 20 ng/ml, obtained no greater than 3 months prior
to randomization.

5. Patient does not meet any of the risk groups outlined in section 3.1.4.

6. Prostate volume greater than 80 cc.

7. Zubrod performance status 2 or greater.

8. Prior total prostatectomy.

9. Prior radiation therapy to the prostate or lower pelvis.

10. Implanted hardware which limits treatment planning or delivery (determined by the
investigator).

11. Chemotherapy within the past 5 years.

12. Diagnosis of an invasive malignancy within 5 years (other than current prostate cancer
or non-metastatic basal or squamous skin cancers or non-metastatic curatively treated
papillary thyroid carcinoma).

13. The use of more than 2 months of androgen deprivation therapy (ADT) prior to
randomization, or plans for ADT to be continued for greater than 6 months.

14. 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). NOTE: If
a method of intrafraction prostate tracking is available which does not require
fiducial markers, this will be adequate for this trial (i.e. 4D transperitoneal
ultrasound, onboard MRI guidance).

15. Unwilling or inability to give informed consent.

16. Not willing to fill out quality of life/psychosocial questionnaires.

17. IPSS score > to 12.

18. Age < 35 and > 85 years.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Northern Sydney Local Health District - Royal North Shore Hospital - St. Leonards
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
Italy
State/province [2] 0 0
Turin

Funding & Sponsors
Primary sponsor type
Other
Name
University of Miami
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Jay L. Friedland MD Prostate Cancer Research Fund
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01794403
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Matthew Abramowitz, MD
Address 0 0
University of Miami
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01794403