MDRT in Prostate Cancer Treated With Long-term Androgen Deprivation Therapy in the STAMPEDE Trial (METANOVA)

NCT06150417 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CASE5823U01CA257638
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out if giving radiation therapy (RT) to areas of metastatic prostate cancer at the time a participant is diagnosed will help control disease better than the usual treatment. This treatment is called metastasis-directed radiotherapy (MDRT). The usual treatment for prostate cancer that has spread to other parts of the body is to give lifelong treatment with hormone therapy (also known as androgen deprivation therapy or ADT). Participants may also be given prostate RT even if the disease is metastatic. Participants will receive hormone therapy (the standard treatment for prostate cancer) for 12 months. The hormone therapy agents may be taken by mouth or given as an injection. Participants will also have prostate RT. Up to 50 participants will have surgery to remove the prostate instead of having prostate RT. A portion of the participants will be randomized to receive MDRT to areas where the cancer has spread. For participants who have surgery to remove their prostate, they will be asked to allow tissue samples collected during the surgery to be sent to an outside lab for research tests and extra blood samples drawn for research tests before starting the study, and at the time the cancer becomes worse if applicable. Participation in the study will last approximately 12 months, and will be followed by their doctor for up to five years per standard of care. The main goal is to compare the efficacy of the standard of care (standard systemic therapy + definitive prostate-directed local therapy) versus the standard of care with metastasis-directed radiotherapy (MDRT) for consolidation of metastatic disease.

Conditions

Prostate Cancer; Malignant Neoplasm of Prostate; Secondary Malignant Neoplasm of Prostate

Keywords

Metastasis-directed Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Failure-free survival (FFS)

  Failure-free survival, defined as time from randomization to first evidence of at least one of: biochemical failure; progression either locally in lymph nodes, or in distant metastases; skeletal related event (where confirmed disease progression);any salvage intervention (local or systemic) required after 12m of planned SOC therapy; or death from prostate cancer. Biochemical failure, based on the PSA nadir in the first 24 weeks after randomization, is defined as at least one of: post-RT: 1. as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3), where PSA must rise by ≥ 25% and ≥ 2ng/mL above nadir, confirmed by progression at two time points at least 3 weeks apart 2. post-RP: serum PSA nadir + 0.4 ng/mL, requiring confirmation ≥4 weeks later

  Up to 5 years from treatment

Secondary Outcomes (16)

• Overall survival (OS)

  Up to 5 years from treatment

• Radiographic progression-free survival (rPFS)

  Up to 5 years from treatment

• Time-to-next-intervention (TTNI)

  Up to 5 years from treatment

• Time-to-castration-resistant prostate cancer

  Up to 5 years from treatment

• Prostate-specific cancer mortality (PCSM)

  Up to 5 years from treatment

Study Arms (2)

Standard of Care (SOC)

ACTIVE COMPARATOR

* Participants will receive the standard of care. Standard systemic therapy (SST) and definitive local therapy (radiotherapy \[RT\] or radical prostatectomy \[RP\]) are the standard of care for de novo oligometastatic prostate cancer. This arm will be used to compare to the experimental arm. * SST will begin 6 weeks of randomization and occur for 12 months. The definitive local therapy will be RT, with a small portion undergoing RP. Local therapy should be completed by the end of Week 20.

Drug: Androgen deprivation therapy (ADT); Drug: Androgen receptor signaling inhibitor (ARSI); Other: Local Therapy: Radical Prostatectomy (RP) or Radiotherapy (RT)

SOC + MDRT

EXPERIMENTAL

* Participants will receive the standard of care. Standard systemic therapy (SST) and definitive local therapy (radiotherapy \[RT\] or radical prostatectomy \[RP\]) are the standard of care for de novo oligometastatic prostate cancer. This arm will be used to compare to the experimental arm. * SST will begin 6 weeks of randomization and occur for 12 months. The definitive local therapy will be RT, with a small portion undergoing RP. Local therapy should be completed by the end of Week 20. * MDRT should be completed by the end of Week 24. Depending on the participant, there are different approaches to MDRT dosing and fraction size.

Drug: Androgen deprivation therapy (ADT); Drug: Androgen receptor signaling inhibitor (ARSI); Other: Local Therapy: Radical Prostatectomy (RP) or Radiotherapy (RT); Radiation: Metastasis directed radiotherapy (MDRT)

Interventions

Androgen deprivation therapy (ADT) DRUG

Standard androgen deprivation therapy (ADT) will be administered at the discretion of treating physician.

SOC + MDRT; Standard of Care (SOC)

Androgen receptor signaling inhibitor (ARSI) DRUG

Standard androgen receptor signaling inhibitors (ARSI) will be administered at the discretion of the treating physician.

SOC + MDRT; Standard of Care (SOC)

Local Therapy: Radical Prostatectomy (RP) or Radiotherapy (RT) OTHER

Local therapy will either be radiotherapy (RT) or radical prostatectomy (RP). * Prostate +/- pelvic nodal radiation * Radical prostatectomy + pelvic lymph node dissection

SOC + MDRT; Standard of Care (SOC)

Metastasis directed radiotherapy (MDRT) RADIATION

In participants randomized to the MDRT arm, MDRT to all lesions will be performed by the end of Week 24. Selection of a particular regimen (the dose and fractionation) will based on the size and location of the participant's metastatic site and the surrounding normal tissue constraints.

SOC + MDRT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years of age.
• Participant must have an ECOG performance status ≤ 1.
• Histologic confirmation of prostate adenocarcinoma of the prostate gland, with evidence of metastasis on imaging by conventional imaging (MRI, CT, or 99mTc bone scan) or PSMA PET/CT. Biopsy of sites of metastasis is strongly encouraged, but not required.
• There must be at least 10-15 unstained slides from 2 cores of the highest tumor cellularity available.
• Newly diagnosed disease with no prior treatment(surgery, radiation or systemic treatment, ie hormone therapy or chemotherapy) to the primary disease.
• Participants may have started LHRH agonist or antagonist therapy, and/or androgen receptor signaling inhibitor (ARSI) as long as it was not started more than 30 days before the participant is enrolled on this study.
• In participants who undergo only conventional imaging, oligometastatic disease is defined as 1-5 discrete metastatic sites in the bone and/or extra-pelvic lymph node (LN) stations.
• Extra-pelvic LN stations are superior to the regional/pelvic LN stations. Pelvic LN stations commence at the bifurcation of the aorta and bifurcation of the proximal inferior vena cava to the common iliac veins.
• Radiographic criteria for a LN to be considered a metastatic focus is defined as short-axis diameter in the axial plane of ≥ 1.0 cm, with irregular border and/or heterogeneous morphology
• In participants who undergo PSMA PET/CT (in the presence or absence of conventional imaging), oligometastatic disease is defined as 1-10 PSMA avid bone lesions and/or extra-pelvic LN stations. The MI-RADS reporting system will be followed to guide PSMA PET interpretation
• In participants extra-pelvic nodal (M1a) disease only by PSMA PET/CT and M0 by conventional imaging (i.e. extra-pelvic LN did not meet size criteria by CT), participant must meet 2 of 3 following criteria in order to be eligible:
• \. PSA ≥ 40
• \. Evidence of cN1 disease (pelvic LN)
• \. Decipher score ≥ 0.89
• Adequate organ and marrow function to receive treatment per treating physician

You may not qualify if:

• Participants with the presence of any of the following:
• Castration resistant prostate cancer (CRPC).
• Evidence of visceral or intracranial metastases.
• Participant receiving any other investigational agents for cancer.
• Participant is participating in a concurrent treatment protocol for cancer.
• Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.
• Prior definitive treatment to the primary prostate cancer or pelvis.
• Participant with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes (HgA1c \> 10), active pituitary or adrenal dysfunction, or psychiatric illness/social situations that would limit compliance with study requirements
• History of another active malignancy within the previous 2 years, except for non-melanoma skin cancer, non-muscle invasive bladder cancer, or a malignancy that is considered cured with minimal risk of recurrence
• Active Crohn's disease or ulcerative colitis despite medical management.
• Refusal to sign informed consent.
• Any condition that in the opinion of the investigator would preclude participation in this study

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Institutes of Health (NIH): collaborator

Study Sites (2)

University Hospitals Cleveland Medical Center Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

Carbone Cancer Center University of Wisconsin-Madison

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Androgen Antagonists; Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics

Study Officials

• Angela Y Jia, MD, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Daniel E Spratt, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  STUDY CHAIR

Central Study Contacts

Angela Y Jia, MD, PhD

CONTACT

216-844-3262; Angela.Jia@UHhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II non-blinded randomized study evaluating men with de novo oligometastatic prostate cancer randomized (1:1) to standard of care (SOC) versus SOC plus MDRT.

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: November 29, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: During study and for 6 months after end of study.
• Access Criteria: OnCore, RedCap.

Locations

US (2)