Clinical trial NCT06111313: The University of Miami Adapt (UAdapt) Trial
Official title: A Phase 2 Risk Adapted Parallel Randomized Trial of MRI-Guided Lattice Stereotactic Focal Radiotherapy of the Prostate With or Without Ultra-Short Term Androgen Deprivation Therapy-The Miami UAdapt Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Varian Medical Systems
First posted: 2023-11-01
Enrollment: 130
Sex: MALE
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Miami UAdapt Trial is a non-comparative phase II study that includes two parallel randomized cohorts that will prospectively assign men radiotherapy (RT) treatment. Patients with relatively favorable risk prostate cancer (PCa) will be eligible for focal therapy LEAD (FTLEAD) RT (n=40), and randomized to receive Lattice Extreme Ablative Dose (LEAD) single high dose RT (SDRT, 12-16 Gy) vs. the same overall plan with the addition of ultrashort-term ADT (uSTADT, 1 month duration) concurrent with SDRT. Higher risk patients are assigned to the HypoLEAD cohort (n=90) and randomized 1:1 to receive Lattice Extreme Ablative Dose (LEAD) single high dose RT (SDRT, 16-20 Gy) followed by moderately hypofractionated (HypoFx) RT for 25 additional fractions vs. the same overall plan with the addition of ultrashort-term ADT (uSTADT, 1 month duration) concurrent with SDRT. In HypoLEAD additional ADT will be assigned at physician discretion per standard of care.
Primary purpose: TREATMENT

Brief summary: The Miami UAdapt Trial is a non-comparative, risk adapted, parallel, randomized, phase 2 study for patients with favorable-intermediate to very high risk non-metastatic prostate cancer with the primary objective of assessing the efficacy and modulation of response of Lattice Extreme Ablative Dose (LEAD) RT with and without androgen deprivation therapy (ADT) at a multidimensional level.


Eligibility criteria: Inclusion Criteria:

1. Biopsy confirmed adenocarcinoma of the prostate (including intraductal adenocarcinoma, excluding small cell carcinoma).
2. T1-T3 disease based on digital rectal exam (DRE), informed by mpMRI. Prostate MRI may aid in the staging evaluation by verifying organ-confined status6,7. The ability to distinguish between organ-confined tumors (≤T2c) and those that extend beyond the prostate (≥T3a) is an important component of treatment decision making.
3. Patients with T3 disease based on DRE, mpMRI, Gleason 8-10, or a PSA of \>15 ng/mL, should undergo a negative metastatic workup prior to signing of consent. A questionable bone scan is acceptable if additional imaging studies; eg, plain x-rays, CT, MRI, prostate specific membrane antigen (PSMA) positron emission tomography (PET)/CT do not confirm for metastasis.
4. No evidence of metastasis by clinical criteria or available radiographic tests (N0M0 by clinical or imaging criteria).
5. Gleason score 6-10.
6. Prostate specific antigen (PSA) ≤100 ng/mL within (≤) 3 months of signing of consent. If PSA was above 100 ng/mL and drops to ≤100 ng/mL with antibiotics, this is acceptable for enrollment.
7. Suspicious peripheral zone or central gland lesion(s) on mpMRI.

   1. Peripheral zone: Distinct lesion on dynamic contrast enhanced (DCE)-MRI with early enhancement and later washout (Note: contrast not required for enrollment), and/or distinct lesion on the apparent diffusion coefficient (ADC) map (Value \<1000).
   2. Central gland: A suspicious central gland lesion on mpMRI must have a distinct lesion on the ADC map (Value \<1000).
8. No previous pelvic radiotherapy.
9. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable).
10. 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.
11. Ability to understand and the willingness to sign a written informed consent document.
12. Zubrod performance status ≤2. Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status may be used to estimate Zubrod.
13. Age ≥35 and ≤85 years at signing of consent.
14. Serum testosterone is within 40% of normal assay limits (eg, x=0.4\*lower assay limit and x=0.4\*upper assay limit + upper assay limit), taken within (≤) 3 months of signing of consent.
15. For patients in HypoLEAD cohort, post-LEAD RT androgen deprivation therapy, including use of secondary agents (eg, abiraterone), is at the discretion of the treating physician but must be declared as none, short-term or long-term prior to enrollment. Note that this ADT regimen differs from the uSTADT regimen. If antiandrogen therapy (eg, bicalutamide) or ADT (LHRH agonist or antagonist injection) is planned, the following restrictions apply:

    1. Anti-androgen therapy and ADT must be started after 3-week post-LEAD RT gradient biopsy.
    2. Anti-androgen therapy and ADT are recommended to be started prior to or concurrent with start of moderately hypofractionated RT course and must be started before the end of the hypofractionated RT course.
    3. The total length planned must be ≤ 30 months.
16. Patient unable to receive iodine or gadolinium contrast due to allergy or poor renal function are still eligible for enrollment.

Exclusion Criteria:

1. Prior pelvic radiotherapy.
2. Prior androgen ablation therapy.
3. Prior or planned radical prostate surgery.
4. Clinical, radiographic, or pathologic evidence of nodal or distant metastatic disease with the following specifications: PSMA-PET or Fluciclovine PET: Patients with subclinical (\<1.5 cm) pelvic lymph nodes that are suspicious on such PET scans will be ineligible for FTLEAD, however will still be eligible for HypoLEAD. In the latter case the treating physician may boost such nodes to a higher dose.
5. 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.
6. Zubrod status \>2.
7. Pretreatment PSA \>100 ng/ml or Gleason score \<6. If PSA was above 100 ng/mL and drops to ≤100 ng/mL with antibiotics, this is acceptable for enrollment.
8. Thyroxine (T4) disease.
9. Patients with impaired decision-making capacity who lack the ability to understand and voluntarily sign a written informed consent document.
10. Patients unable to tolerate diagnostic MRI acquisition. Note: inability to tolerate contrast agents is not exclusionary.

Primary outcomes:
measure: Proportion of Patients with Biochemical Disease Failure (FFBN9mo)
timeFrame: Up to 14 Months
measure: Proportion of Patients with Clinical Disease Failure
timeFrame: Up to 14 Months
Secondary outcomes:
measure: Proportion of Patients with Biochemical Disease Failure (Phoenix definition)
timeFrame: Up to 2.5 years
measure: Proportion of Patients with Clinical Disease Failure
timeFrame: Up to 2.5 years
measure: Proportion of Patients with Pathology-determined complete response (PathCR)
timeFrame: Up to 2.0-2.5 years after all treatment
measure: Proportion of Patients with Pathology-determined complete response (PathCR)
timeFrame: Up to 2.5 year
measure: Incidence of Failure rate (FR)
timeFrame: Up to 2.5 years
measure: Number of Treatment Related Acute toxicity
timeFrame: Up to 3 months
measure: Number of Treatment Related Late toxicity
timeFrame: Up to 8 Years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Benjamin Spieler, MD
role: PRINCIPAL_INVESTIGATOR
References: