Overview

This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for Veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.

Eligibility

Inclusion Criteria:

        Age 18 years. Ability to provide Informed Consent for participation in the study ECOG
        Performance Status 2 at time of enrollment. Prostate cancer, confirmed histologically or
        cytologically. If original documentation of histology and cytology are not available,
        documentation of prostate cancer satisfies these criteria. If recurrent, prior
        curative-intent local therapy to all sites of prostate cancer with either upfront
        radiotherapy or prostatectomy with or without post-operative radiotherapy.
        If recurrent, PSA suspicious for biochemical recurrence after local therapy, with lab
        value(s) taken prior to start of SST (if current SST has already started) or within 90 days
        prior to enrollment if not already on SST, and meeting one of the three below categories:
        PSA 0.2 ng/ml x 2 after prostatectomy +/- post-operative radiotherapy; Elevation of PSA 2
        ng/ml above the nadir after definitive radiotherapy; Or Two consecutively elevated PSAs
        with evidence of metastasis on the imaging Studies.
        -Serum testosterone obtained prior to randomization based on one of the criteria below:
        For patients who have a history of a prior episode of therapy with SST agents for prostate
        cancer, a total testosterone 100 ng/dl after completion of the prior episode of SST and
        before the start of current SST or within 30 days of starting current SST if the patient
        has already started SST for recurrence.
        For patients who have no prior history of an episode of therapy with SST agents and have
        already started SST for recurrence, this pre-SST testosterone is not required.
        CT or MRI abdomen/pelvis performed prior to start of SST (if current SST has already
        started) or within 90 days prior to enrollment if not already on SST. The results from the
        CT component of the PET/CT can be used to fulfill this criterion. This is optional for
        patients who have a PSMA PET/CT. Yechnetium (Tc99m-MDP) or sodium fluoride (NaF) bone scan
        (sodium fluoride preferred) performed prior to start of SST (if current SST has already
        started), or within 90 days prior to enrollment if not already on SST. This is optional for
        patients who have a PSMA PET/CT. Prostate PET/CT (currently PSMA, Fluciclovine, choline)
        performed prior to start of SST (if current SST has already started), or within 90 days
        prior to enrollment if not already on SST.
        1-10 lesions suspicious for nodal recurrence or metastasis from prostate cancer as
        determined by the investigator based on the above imaging studies.
        Has already undergone NPOP sequencing or a plan is in place for NPOP sequencing for
        prostate cancer.
        For participants on SST at the time of enrollment only:
        Has been on SST for 180 days. For participants with local recurrence after curative-intent
        local therapy on imaging :
        Patients with local recurrence in the prostate, SV, or prostate bed are eligible as long as
        there is at least 1 nodal or distant metastatic recurrence. Biopsy must confirm local
        recurrence for patients who have had prior curative-intent radiation to the prostate, SV,
        or prostate bed.
        Candidate for salvage local therapy (refer to Section 10.4) as determined by a urologist or
        radiation oncologist (depending on the respective modality to be used to treat the local
        recurrence).
        For participants with de novo prostate cancer:
        Candidate for prostate-directed radiation.
        Exclusion Criteria:
          -  Any current or prior evidence of castration-resistant prostate cancer, defined as two
             consecutive rises in serum PSA, obtained at a minimum of 1-week interval, with the
             final PSA value >/= 1 ng/ml, while having a total testosterone < 50 ng/dl).
          -  Prior malignancy, except the following:
               -  Adequately treated non-melanomatous skin cancer;
               -  Adequately treated Stage 0, I, or II cancer from which the patient is currently
                  in complete remission; or
               -  Any other cancer from which the patient has been disease free for three years.
          -  Presence of a symptomatic metastasis that requires palliative radiotherapy.
          -  Any known brain metastases, presence of leptomeningeal disease, malignant spinal cord
             compression, or malignant cauda equina syndrome.
          -  Prior nodal, bone, or visceral metastasis after curative-intent therapy other than
             those identified on the enrollment imaging studies which make the patient ineligible
             for PET-directed local therapy (per investigator discretion).
          -  Prior radiation therapy to any sites requiring PET-directed local therapy or salvage
             local therapy that will lead to prohibitively high risk of toxicity from subsequent
             local therapy, as determined by the treating radiation oncologist (if radiation is
             intended as the study local therapy) or surgeon/urologist (if surgery is intended as
             the study local therapy).
          -  Any other previous or current condition, which, in the judgement of the LSI, is likely
             to interfere with any STARPORT treatments or assessments.