This phase II trial studies the effect of an extra high dose radiation treatment (boosts) to the magnetic resonance imaging (MRI) defined high risk tumor areas, in addition to the standard radiation therapy in treating patients with prostate cancer. It will examine the effect of this treatment in controlling prostate cancer growth and preserving quality of life by reducing radiation dose to the nearby organs at risk around the prostate. Additionally, it will establish the relationship of pre- and post-treatment MRI to MRI-directed biopsy results at 2-2.5 years after treatment. External beam radiation treatment of the prostate for prostate cancer is a common primary treatment alternative to prostate surgery that allows for preservation of anatomy and the potential for better functional outcome. Even though radiation treatments are effective there is evidence that giving higher radiation doses to the prostate will result in further significant gains in controlling cancer. However, higher radiation doses to the entire prostate are associated with an increased risk of side effects. Stereotactic lattice radiotherapy and hypofractionated radiotherapy are treatments designed to deliver a high dose boost of radiation to regions of the prostate indicated to have a tumor based on newer magnetic resonance imaging methods. This trial may help researchers determine if stereotactic lattice radiotherapy boost works better than hypofractionated radiotherapy boost in treating patients with prostate cancer when given in addition to standard radiotherapy.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02307058.
PRIMARY OBJECTIVE:
I. To compare the rate of the Combined Early Freedom Froom Failure (CEFFF) Endpoint of Freedom from the biochemical nadir thresholds at 9 months (FFBN9mo), defined as prostate-specific antigen (PSA) @ 9 months of ≤ 1.5 for radiation therapy (RT) alone and ≤ 0.1 for RT+ androgen deprivation therapy (ADT) plus prostate tumor pathologic complete response (PathCR) by prostate biopsies 2-2.5 years after completion of all planned treatment (radiotherapy and androgen deprivation therapy) between two multiparametric (MP)-magnetic resonance imaging (MRI)-defined tumor radiotherapy boost methods (from the Miami lattice extreme ablative dose [LEAD] and hypofractionated extended image-guided highly targeted [HEIGHT] trials).
SECONDARY OBJECTIVES:
I. To establish the relationship between CEFFF and changes in serial post-RT MRI's obtained at 3 months and 9 months after RT, and within 3 months prior to the primary endpoint post-treatment prostate biopsy at 2.0-2.5 years (yr) after completion of all therapy.
II. To evaluate and compare acute and late toxicity.
III. To compare pretreatment and posttreatment Health-Related Quality of Life (HRQOL) between the arms.
IV. To quantify gene/biomarker expression in different MP-MRI prostate tumor regions (habitats) and to relate developed habitat signatures to MP-MRI changes, CEFFF, and other secondary clinical outcome endpoints.
V. To determine biochemical failure (nadir+2, Phoenix definition), clinical (local, regional, or distant) failure, cause specific mortality, and overall mortality rates.
VI. To evaluate the numbers, viability, and gene expression of circulating tumor cells (CTC’s) pretreatment and at different posttreatment intervals (same as for post-treatment MRIs).
VII. To draw and store serum, plasma and buffy coat from pretreatment and at different posttreatment intervals (same as for post-treatment MRIs) for future studies.
EXPLORATORY OBJECTIVE:
I. To assess when possible the pretreatment and post-treatment changes in axumin or prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), and compare to MRI changes and patient outcome.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (LEAD): Patients undergo stereotactic lattice radiation therapy consisting of a one-time high dose boost first radiation treatment, and then 38 fractions of radiation over 15 minutes each for 5 days per week for approximately 8 weeks in the absence of disease progression or unacceptable toxicity.
ARM II (HEIGHT): Patients undergo moderate hypofractionated radiation therapy over 38 fractions for 5 days per week for approximately 7.5 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3 and 9 months, then every 6-12 months for up to 5.25 years.
Lead OrganizationUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
Principal InvestigatorAlan Pollack
