MDRT in Prostate Cancer Treated With Long-term Androgen Deprivation Therapy in the STAMPEDE Trial (METANOVA)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorCase Comprehensive Cancer Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Androgen deprivation therapy (ADT)
DrugStandard androgen deprivation therapy (ADT) will be administered at the discretion of treating physician.
Androgen receptor signaling inhibitor (ARSI)
DrugStandard androgen receptor signaling inhibitors (ARSI) will be administered at the discretion of the treating physician.
Local Therapy: Radical Prostatectomy (RP) or Radiotherapy (RT)
Other interventionLocal therapy will either be radiotherapy (RT) or radical prostatectomy (RP). * Prostate +/- pelvic nodal radiation * Radical prostatectomy + pelvic lymph node dissection
Metastasis directed radiotherapy (MDRT)
RadiationIn 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.
Treatment groups
200 Participants
are divided into 2 treatment groupsGroup A: Standard of Care (SOC)Active comparator 3 interventions
Group B: SOC + MDRTExperimental treatment 4 interventions
Trial outcomes
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
Time frame
Up to 5 years from treatmentSecondary outcomes
1
Overall survival (OS)
Overall Survival (OS) is defined as the time from randomization until death due to any cause. For participants who survive, time to death will be censored at the time of last contact. The distributions of OS for each treatment arm will be plotted using the Kaplan-Meier method, and median values for each will be estimated and reported with 95% CIs for each treatment arm and compared using stratified log-rank tests. Univariable Cox proportional hazard models will be used to estimate the effect of MDRT on OS.
Time frame
Up to 5 years from treatment2
Radiographic progression-free survival (rPFS)
Radiographic progression-free survival (rPFS) is defined as the time from randomization until clinical progression, detection of at least one new metastatic lesion on CT, MRI, bone scan or Prostate Specific Membrane Antigen (PSMA) PET, or death from prostate cancer. The distributions of rPFS for each treatment arm will be plotted using the Kaplan-Meier method, and median values for each will be estimated and reported with 95% CIs for each treatment arm and compared using stratified log-rank tests. Univariable Cox proportional hazard models will be used to estimate the effect of MDRT on rPFS.
Time frame
Up to 5 years from treatment3
Time-to-next-intervention (TTNI)
TTNI is defined as time-to-next-intervention. TTNI will be summarized in each arm and compared using Chi-square tests, as well as time-to-event analyses using cumulative incidence methods.
Time frame
Up to 5 years from treatment4
Time-to-castration-resistant prostate cancer
The rate of time-to-castration-resistant prostate cancer will be summarized in each arm and compared using Chi-square tests, as well as time-to-event analyses using cumulative incidence methods.
Time frame
Up to 5 years from treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Case Comprehensive Cancer Center
Lead sponsor
National Institutes of Health (NIH)
Collaborator
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov