Clinical trial NCT04402151: Study of PSMA PET/MR Guided Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost (SBRT-SIB) for High-Intermediate and High Risk Prostate Cancer
Official title: Single-Arm Phase II Study of PSMA PET/MR Guided Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost (SBRT-SIB) for High-Intermediate and High Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-05-26
Enrollment: 50
Sex: MALE
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm Phase II clinical trial assessing the clinical efficacy of prostate specific membrane antigen (PSMA) PET/MR guided MR-LINAC based SBRT-SIB with planned accrual of 50 patients.

Detailed description: Localized prostate cancer can be treated in 5 sessions using a precise, targeted form of radiation known as stereotactic body radiation therapy (SBRT), with low toxicity. Despite these advances, overall outcomes for aggressive (high risk) prostate cancer remain poor, with 10-year recurrence-free survival of approximately 65% regardless of treatment modality. Recurrences are typically distant and carry poor prognosis, with 5 year survival of 25%. The investigators propose to utilize the latest advances in cancer imaging (PSMA Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MR)) and radiation delivery (MR-guided radiation therapy with real-time adaptive planning), to deliver a personalized radiation treatment that targets the areas of greatest risk of recurrence in the prostate with improved precision, and as a result improve clinical outcomes for individuals with high risk prostate cancer. PSMA PET/MR is a novel imaging modality, not yet widely available, that augments the tissue detail provided by MR. The combination of PSMA PET with MR results in improved delineation of intraprostatic nodules and higher diagnostic accuracy for detection of metastatic disease compared to conventional imaging. PSMA PET/MR imaging data is readily transferable to a MR-based linear accelerator (MR-LINAC), a novel, innovative platform that allows direct visualization of the tumor during treatment, and permits real-time individualized correction for motion with online adaptive radiation planning.

Eligibility criteria: Inclusion Criteria:

* Male aged 21 years or older.
* Ability to provide signed informed consent and willingness to comply with protocol requirements.
* Pathologic confirmation of high-risk adenocarcinoma of the prostate gland as follows: a. Gleason 8-10 or tertiary component 5 disease and/or b. PSA of 20 ng/ml or greater and/or c. Tumor stage of T2c or greater; OR Unfavorable intermediate risk (Gleason 4+3=7, \>50% of cores involved, or 2 or more intermediate risk factors which include Gleason 7 disease, PSA 10-20, or T2b disease)
* Participants must agree to use an acceptable form of birth control and utilize condoms for a period of seven days after each PSMA injection, if engaged in sexual activity.
* No evidence of metastatic disease, including pelvic lymph nodes.

Exclusion Criteria:

* Clinical and/or technical factors that would compromise statistical analysis of the PET and/or MR.
* Contraindications to PSMA IV administration
* Contraindications to prostate SBRT (history of transurethral resection of prostate; prostate size greater than 150 cc; AUA score greater than 20; history of prior radiation to the prostate)
* Other unspecified reasons that, in the opinion of investigators, make the subject unsuitable for enrollment
* Patients on or intending to take abiraterone will be excluded

Primary outcomes:
measure: Clinical efficacy of prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR), MR-Linear Accelerator (LINAC) will be assessed by evaluating recurrence free survival
timeFrame: 24 months
Secondary outcomes:
measure: Performance of PSMA PET/MR to MR alone at staging prostate cancer
timeFrame: Baseline
measure: Performance of PSMA PET/MR to MR alone for identification of dominant intraprostatic nodules during radiation planning
timeFrame: Baseline
measure: Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA
timeFrame: Baseline
measure: Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA
timeFrame: 12 months
measure: Change in Quality of life questionnaires (EPIC-26) will be assessed.
timeFrame: Baseline, 1month, 6months, 12 months, 18 months and 24 months.
measure: Change in The American Urological Association (AUA) symptom score
timeFrame: Baseline, 1month, 6months, 12 months, 18 months and 24 months.
measure: Change in Number of Subjects with Adverse events
timeFrame: Baseline, 1month, 6months, 12 months and 24 months.
measure: The change in radiation doses received by the surrounding normal structures/PTV for each initial and adapted plan will be analyzed with a signed-rank Wilcoxon test (non-parametric test for paired comparisons).
timeFrame: Baseline, 1month
measure: Compare the changes in the Microbiome during SBRT-SIB
timeFrame: Baseline
measure: Compare the changes in the Microbiome during SBRT-SIB
timeFrame: approx. 3 weeks
measure: Compare the changes in the Microbiome during SBRT-SIB
timeFrame: 12 months
measure: Compare the immunological changes during SBRT-SIB
timeFrame: Baseline
measure: Compare the immunological changes during SBRT-SIB
timeFrame: approx. 3 weeks
measure: Compare the immunological changes during SBRT-SIB
timeFrame: 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Silvia Formenti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: