Clinical trial NCT01411332: Hypofractionated Image-Guided Radiotherapy For Prostate Cancer: The HEIGHT Trial
Official title: A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Prostate Adenocarcinoma
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2011-08-08
Enrollment: 18
Sex: MALE
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Biopsy Failure
timeFrame: Up to 2.25 years
Secondary outcomes:
measure: Toxicity Rate
timeFrame: Up to 6 years
measure: Mortality
timeFrame: Up to 6 years
measure: Failure Rate
timeFrame: Up to 6 years
measure: EPIC SF-12 Scores
timeFrame: 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).
measure: MAX-PC Scores
timeFrame: 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)
measure: Biomarker Expression in Prostate Tumor Regions
timeFrame: Up to 3 years
measure: Incidence of Circulating Free DNA
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Alan Pollack, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: