Hypofractionated Image-Guided Radiotherapy For Prostate Cancer: The HEIGHT Trial (HEIGHT)

• ClinicalTrials.gov Identifier: NCT01411332
• Recruitment Status: Completed
• First Posted: August 8, 2011
• Results First Posted: July 30, 2021
• Last Update Posted: May 22, 2023
• Sponsor: University of Miami
• Information provided by (Responsible Party): Alan Pollack, MD, PhD, University of Miami

Study Description

Brief Summary:

1. Delivery of directed hypofractionated targeted (HT) radiotherapy (RT) tumor boost to the dominant tumor lesion in the prostate as identified by multiparametric MRI will increase tumor eradication from the prostate.
2. Biomarker expression levels differ in the multiparametric MRI defined regions at high risk of harboring tumors that determine outcome.
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 or disease	Intervention/treatment	Phase
Prostate Cancer; Prostate Adenocarcinoma	Radiation: SIMRT; Radiation: HTIMRT	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
• Actual Study Start Date: October 31, 2011
• Actual Primary Completion Date: July 11, 2017
• Actual Study Completion Date: November 22, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm I: SIMRT; 'Participants in this group will receive the Standard Fractionated Intensity Modulated Radiotherapy (SIMRT) consisting 40 fractions over 8 weeks.	Radiation: SIMRT; A total dose of 80 Gy will be delivered in 40 fractions to the Clinical Target Volume (CTV).; Other Name: Standard Fractionated Intensity Modulated Radiotherapy
Active Comparator: Arm II: HTIMRT; Participants in this group will receive the Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT) consisting of 38 fractions over 7.5 weeks.	Radiation: HTIMRT; Dose escalation to the Multiparametric MRI (MP-MRI) by dose painting at 2.35-2.40 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 89.3-91.2 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 95.5 Gy in 2.0 Gy fractions.; Other Name: Hypofractionated Targeted Intensity Modulated Radiotherapy

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Biopsy Failure [ Time Frame: Up to 2.25 years ]
   Number of participants showing positive prostate biopsy finding post treatment.

Secondary Outcome Measures :

1. Toxicity Rate [ Time Frame: Up to 6 years ]
   Toxicity rate will be reported as the number of participants experiencing any treatment-related adverse events. Acute and Late Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Acute toxicity will be defined as any treatment-related adverse event during and within 3 months of completing treatment. Late Toxicity will be defined as any treatment-related adverse events occurring more than 3 months after treatment completion.
2. Mortality [ Time Frame: Up to 6 years ]
   Mortality will be reported as overall survival and failure free survival. Overall survival is defined as the elapsed time from start of radiotherapy to death from any cause. Failure free survival is defined as 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.
3. Failure Rate [ Time Frame: Up to 6 years ]
   Failure rate will be reported as the incidence of biochemical or clinical failure. Biochemical failure is defined is an increase of 2 or greater from nadir of Prostate Specific Antigen (PSA) levels. Clinical Failure is defined as newly identified extension outside the prostate after initial regression, or urinary obstructive symptoms with carcinoma or regional/distant failure due to radiographic evidence metastasis.
4. EPIC SF-12 Scores [ Time Frame: At baseline, at last week of treatment (Up to 8 weeks), at 6 weeks after treatment (Up to 14 weeks), at 3 months after treatment (Up to 20 weeks), at 9 months after treatment (Up to 44 weeks). ]
   Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
5. MAX-PC Scores [ Time Frame: At baseline, at last week of treatment (Up to 8 weeks), at 6 weeks after treatment (Up to 14 weeks), at 3 months after treatment (Up to 20 weeks), at 9 months after treatment (Up to 44 weeks) ]
   Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC). The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
6. Biomarker Expression in Prostate Tumor Regions [ Time Frame: Up to 3 years ]
   The amount of biomarker expression will be evaluated via immunohistochemistry (IHC) from ultrasound guided prostate biopsy tissue samples for both functional MRI suspicious regions and those that are not suspicious.
7. Incidence of Circulating Free DNA [ Time Frame: Up to 3 years ]
   Incidence of circulating free DNA, as assessed from blood samples.

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• A. Biopsy confirmed adenocarcinoma of the prostate.

• B. T1-T3a disease based on digital rectal exam.

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

• E. Patients with Gleason score 8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 (±2 months) 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 recommended to begin after fiducial marker placement, if applicable; however, ADT is permitted to have been started up to two months prior to the signing of consent.

  1. Patients with Gleason score 8 disease must have <40 of the diagnostic tumor tissue involved with tumor.
  2. Patients with Gleason score ≤7 may be treated with 4-6 (±2 months) months of ADT.
• F. PSA ≤100 ng/mL within 3 months of enrollment. If PSA was above 100 and dropped to ≤100 with antibiotics, this is acceptable for enrollment.
• G. If PSA is >15 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, CT and/or MRI are negative for metastasis.
• H. No previous pelvic radiotherapy
• I. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable)
• J. 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.

• K. Identifiable multiparameter functional MRI defined tumor lesion or lesions using a 1.5T or 3.0T MRI (3.0T preferable), that total in volume <33% of the prostate within 3 months prior to enrollment.

  a. Multiparametric functional including diffusion weighted imaging (DWI) of prostate and pelvis is required prior to protocol consideration

• L. Ability to understand and the willingness to sign a written informed consent document
• M. Zubrod performance status <2 (Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status may be used to estimate Zubrod)
• N. Willingness to fill out quality of life/psychosocial forms.
• O. Age ≥35 and ≤85 years.
• P. 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),, 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.
• Q. Serum liver function tests (LFTs) taken within 3 months of enrollment.
• R. Complete blood counts taken within 3 months of enrollment.

Exclusion Criteria

• A. Previous pelvic radiotherapy.
• B. Previous history of radical prostatectomy.
• C. 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
• D. Not willing to fill out quality of life/psychosocial questionnaires.

Contacts and Locations

Locations

United States, Florida

University of Miami

Miami, Florida, United States, 33136

Sponsors and Collaborators

University of Miami

Investigators

• Principal Investigator: Alan Pollack, MD, PhD; University of Miami

  Study Documents (Full-Text)

Documents provided by Alan Pollack, MD, PhD, University of Miami:

Study Protocol and Statistical Analysis Plan  [PDF] March 30, 2016

More Information

• Responsible Party: Alan Pollack, MD, PhD, Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT01411332
• Other Study ID Numbers: 20100635
• First Posted: August 8, 2011
• Results First Posted: July 30, 2021
• Last Update Posted: May 22, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases