Trial Title:
The University of Miami Adapt (UAdapt) Trial
NCT ID:
NCT06111313
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Androgens
Relugolix
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
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
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
FTLEAD
Description:
In focal therapy lattice extreme ablative (FTLEAD) RT, the multiparametric-MRI (mpMRI)
defined gross tumor volume (GTV) will receive 16-20 Gy in a single fraction of RT to the
targeted area which is the tumor within the prostate, with or without uSTADT.
Arm group label:
Focal Therapy lattice extreme ablative dose (FTLEAD), RT Only, Arm A
Arm group label:
Focal Therapy lattice extreme ablative dose (FTLEAD), uSTADT, Arm B
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), Arm C
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), uSTADT, Arm D
Intervention type:
Drug
Intervention name:
Ultra-Short-Term Androgen Deprivation Therapy with Relugolix
Description:
Ultra-Short-Term Androgen Deprivation Therapy (uSTADT) is hormone therapy that includes
Relugolix. Patients will receive a loading dose of uSTADT for a total duration 4 weeks
(28 days), with oral LHRH antagonist relugolix administered daily starting 2 weeks prior
to LEAD RT and continuing until 2 weeks afterwards as per Study Calendar. Patients
randomized to uSTADT will receive a loading dose of 360 mg of oral relugolix on Day 14
followed by 120 mg of oral relugolix daily from Day 13 to Day 14. Patients will be
instructed to take relugolix orally once daily at approximately the same time each day.
Patients may take relugolix with or without food and should swallow tablets whole and not
crush or chew tablets.
Arm group label:
Focal Therapy lattice extreme ablative dose (FTLEAD), uSTADT, Arm B
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), uSTADT, Arm D
Intervention type:
Radiation
Intervention name:
HypoLEAD
Description:
In Hypofractionated LEAD (HypoLEAD), the multiparametric-MRI (mpMRI) defined GTV will
receive 12-16 Gy in a single fraction on the first day of treatment, with or without
uSTADT. Four weeks after LEAD RT, patients will begin whole prostate moderately hypoLEAD
(67.5 Gy in 25 fractions) with pelvic nodal irradiation and further ADT at the discretion
of the treating physician.
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), Arm C
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), uSTADT, Arm D
Intervention type:
Drug
Intervention name:
ADT Standard of Care
Description:
Participants will receive ADT as per standard of care (SOC).
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), Arm C
Arm group label:
Lattice extreme ablative dose followed by hypofractionated RT (HypoLEAD), uSTADT, Arm D
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.
Criteria for 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.
Gender:
Male
Minimum age:
35 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Contact:
Last name:
Benjamin Spieler, MD
Phone:
305-243-4229
Email:
bxs737@med.miami.edu
Investigator:
Last name:
Benjamin Spieler, MD
Email:
Principal Investigator
Start date:
October 1, 2024
Completion date:
October 1, 2032
Lead sponsor:
Agency:
University of Miami
Agency class:
Other
Collaborator:
Agency:
Varian Medical Systems
Agency class:
Industry
Source:
University of Miami
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06111313
