MRI-Guided LEAD Stereotactic Radiotherapy with or without Ultra-Short Term Androgen Suppression Therapy for the Treatment of Prostate Cancer, the Miami UAdapt Trial

Status: active

This phase II trial tests how well magnetic resonance imaging (MRI)-guided lattice extreme ablative dose (LEAD) stereotactic body radiotherapy (SBRT) with or without ultra-short term androgen suppression therapy (uSTAS) works in treating patients with prostate cancer. Stereotactic body radiotherapy (SBRT) is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). This type of radiation therapy helps spare normal tissue. Focal therapy LEAD (FTLEAD) RT, a single dose of SBRT, uses multiparametric-MRI (mpMRI) imaging to identify the areas of tumor in order to deliver radiation to only the areas of tumor within the prostate. Androgen deprivation therapy (ADT) is treatment to suppress or block the production or action of male hormones, and uSTAS is treatment over 1 month. Darolutamide,, a type of ADT, may lower the amount of testosterone made by the body, or block the use of testosterone by the tumor cells. This may help stop the growth of tumor cells that need testosterone to grow. Giving FTLEAD RT with or without uSTAS may be effective in treating the tumor within the prostate and decrease the impact on quality of life in prostate cancer patients. This trial also evaluates the effectiveness of FTLEAD RT followed by hypofractionated LEAD (HypoLEAD) RT to the entire prostate in higher risk patients. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving FTLEAD RT followed by HypoLEAD RT to the entire prostate may improve disease control while reducing side effects and maintaining quality of life in higher-risk prostate cancer patients.

Inclusion Criteria

Biopsy confirmed adenocarcinoma of the prostate (including intraductal adenocarcinoma, excluding small cell carcinoma)
T1-T3 disease based on digital rectal exam (DRE) and/or mpMRI. Prostate MRI may aid in the staging evaluation by verifying organ-confined status. 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
Patients with T3 disease based on DRE, mpMRI, Gleason 8-10, or a prostate specific antigen (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, PSMA PET/CT) do not confirm for metastasis
No evidence of distant metastasis by clinical criteria or available radiographic tests (M0 by clinical or imaging criteria)
Gleason score 6-10
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
Suspicious peripheral zone or central gland lesion(s) on mpMRI * 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) * Central gland: A suspicious central gland lesion on mpMRI must have a distinct lesion on the ADC map (value < 1000)
No previous pelvic radiotherapy
No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable)
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
Ability to understand and the willingness to sign a written informed consent document
Zubrod performance status ≤ 2. (Karnofsky or Eastern Cooperative Oncology Group [ECOG] performance status may be used to estimate Zubrod)
Age ≥ 35 and ≤ 85 years at signing of consent
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
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 uSTAS regimen. If antiandrogen therapy (eg, bicalutamide) or ADT (LHRH agonist or antagonist injection) is planned, the following restrictions apply: * Anti-androgen therapy and ADT must be started after 3-week post-LEAD RT gradient biopsy * 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 * The total length planned must be ≤ 30 months
Patient unable to receive iodine or gadolinium contrast due to allergy or poor renal function are still eligible for enrollment

Exclusion Criteria

Prior pelvic radiotherapy
Prior androgen ablation therapy
Prior or planned radical prostate surgery
Clinical, radiographic, or pathologic evidence of nodal or distant metastatic disease with the following specifications: PSMA-PET or fluciclovine F18 ([18F] 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
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
Zubrod status > 2
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
Thyroxine (T4) disease (checked by review of patient history)
Patients with impaired decision-making capacity who lack the ability to understand and voluntarily sign a written informed consent document
Patients unable to tolerate diagnostic MRI acquisition. Note: inability to tolerate contrast agents is not exclusionary

Additional locations may be listed on ClinicalTrials.gov for NCT06111313.

United States

Florida

Coral Gables

UM Sylvester Comprehensive Cancer Center at Coral Gables

Status: Active

Contact: Benjamin Spieler

Phone: 305-243-4229

Email: Bxs737@med.miami.edu

Deerfield Beach

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Status: Active

Contact: Benjamin Spieler

Phone: 305-243-4229

Email: Bxs737@med.miami.edu

Miami

University of Miami Miller School of Medicine-Sylvester Cancer Center

Status: Active

Contact: Benjamin Spieler

Phone: 305-243-4229

Email: bxs737@med.miami.edu

Plantation

UM Sylvester Comprehensive Cancer Center at Plantation

Status: Active

Contact: Benjamin Spieler

Phone: 305-243-4229

Email: Bxs737@med.miami.edu

PRIMARY OBJECTIVE:

I. To determine proportion of patients with biochemical and/or clinical disease failure @ 1 year (BCDF1) after completion of RT.

SECONDARY OBJECTIVES:

I. To determine proportion of patients with biochemical and/or clinical disease failure @ 2.0-2.5 yrs. (BCDF2) after completion of all treatment (all treatment includes both RT and ADT, whichever is longer).

II. To assess acute toxicity.

III. To assess late toxicity.

EXPLORATORY OBJECTIVES:

I. To assess biochemical failure-free interval (BFFI).

II. To assess biochemical failure-free Survival (BFFS).

III. To assess failure-free interval (FFI).

IV. To assess failure-free survival (FFS).

V. To determine proportion of patients with pathology-determined complete response (PathCR).

VI. To assess failure rate (FR).

VII. To assess progression-free survival (PFS).

VIII. To assess overall survival (OS).

IX. To assess pretreatment, post-treatment, and longitudinal health-related quality of life (HRQoL).

X. To draw and store tumor and benign prostate tissue, urine, serum, plasma, and buffy coat from pretreatment and at different post-treatment intervals for future studies.

XI. To assess the ability of a software application “HRS6” to identify clinically significant prostate cancer both at the time of prostate biopsy and in the radiotherapy planning process.

OUTLINE: Patients with very low risk to favorable intermediate risk clinical genomic (CG) score are assigned to Cohort 1. Patients with unfavorable intermediate to very high-risk CG score are assigned to Cohort 2. Patients are randomized to 1 of 2 arms within each cohort. Patients randomized to Arm B and Arm D are further randomized to 1 of 2 arms.

COHORT 1 (FTLEAD):

ARM A (LEAD RT ALONE): Patients undergo mpMRI guided FTLEAD RT on day 1. Additionally, patients undergo digital rectal exam (DRE), blood sample collection, prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), mpMRI, and prostate biopsy throughout the study. Patients may also undergo DRE at screening and bone scan at screening and at progression.

ARM B1 (LEAD RT + uSTAS): Patients undergo mpMRI guided FTLEAD RT on day 1. Patients also receive darolutamide orally (PO) twice daily (BID) on days -14 to 14 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo DRE, blood sample collection, PSMA PET/CT, mpMRI, and prostate biopsy throughout the study. Patients may also undergo DRE at screening and bone scan at screening and at progression.

ARM B2 (LEAD RT + uSTAS): Patients undergo mpMRI guided FTLEAD RT on day 1. Patients also receive darolutamide PO BID on days -28 to 0 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo DRE, blood sample collection, PSMA PET/CT, mpMRI, and prostate biopsy throughout the study. Patients may also undergo DRE at screening and bone scan at screening and at progression.

COHORT 2 (HypoLEAD):

ARM C (HypoLEAD): Patients undergo mpMRI guided FTLEAD RT on day 1. Beginning 4 weeks later, patients undergo HypoLEAD RT over 15 minutes QD on Monday-Friday for up to 25 fractions over 5 weeks. Patients may also receive ADT post-uSTAS at the discretion of the treating physician. Additionally, patients undergo DRE, blood sample collection, PSMA PET/CT, mpMRI, and prostate biopsy throughout the study. Patients may also undergo DRE at screening and bone scan at screening and at progression.

ARM D1 (HypoLEAD + uSTAS): Patients undergo mpMRI guided FTLEAD RT on day 1. Beginning 4 weeks later, patients undergo HypoLEAD RT over 15 minutes QD on Monday-Friday for up to 25 fractions over 5 weeks. Patients also receive darolutamide PO BID on days -14 to 14 in the absence of disease progression or unacceptable toxicity. Patients may also receive ADT post-uSTAS at the discretion of the treating physician. Additionally, patients undergo DRE, blood sample collection, PSMA PET/CT, mpMRI, and prostate biopsy throughout the study. Patients may also undergo DRE at screening and bone scan at screening and at progression.

ARM D2 (HypoLEAD + uSTAS): Patients undergo mpMRI guided FTLEAD RT on day 1. Beginning 4 weeks later, patients undergo HypoLEAD RT over 15 minutes QD on Monday-Friday for up to 25 fractions over 5 weeks. Patients also receive darolutamide PO BID on days -28 to 0 in the absence of disease progression or unacceptable toxicity. Patients may also receive ADT post-uSTAS at the discretion of the treating physician. Additionally, patients undergo DRE, blood sample collection, PSMA PET/CT, mpMRI, and prostate biopsy throughout the study. Patients may also undergo DRE at screening and bone scan at screening and at progression.

After completion of study treatment, patients are followed up at 6 weeks, and months 3, 9, 12, 27 then every 6 months until month 60.

Have a question?
We're here to help

Chat with us: LiveHelp
Call us: 1-800-4-CANCER
(1-800-422-6237)

Which trials are right for you?

Use the checklist in our guide to gather the information you’ll need.

MRI-Guided LEAD Stereotactic Radiotherapy with or without Ultra-Short Term Androgen Suppression Therapy for the Treatment of Prostate Cancer, the Miami UAdapt Trial

Description

Eligibility Criteria

Locations & Contacts

Trial Objectives and Outline

Trial Phase & Type

Lead Organization

Trial IDs

Have a question?We're here to help

Which trials are right for you?

Have a question?
We're here to help