Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for OligoRecurrenT Prostate Cancer

  • STATUS
    Recruiting
  • End date
    Dec 1, 2025
  • participants needed
    464
  • sponsor
    VA Office of Research and Development
Updated on 21 August 2021

Summary

The primary goal of this study is to determine if adding PET-directed local therapy improves disease control compared to standard systemic therapy alone in Veterans with oligorecurrent prostate cancer on PET/CT. The investigators will conduct a multi-institutional phase II/III randomized trial comparing SST with or without PET-directed local therapy using radiation or surgery to all metastases and if a local recurrence is present.

Description

Prostate Cancer is the most commonly diagnosed cancer among Veterans, comprising 30% of new cancer diagnoses in the VA. Eighty-five percent of men present with localized prostate cancer, which is typically treated with active surveillance or curative local therapy using surgery or radiation therapy. Unfortunately, twenty percent of Veterans undergoing curative local therapy will develop metastatic recurrence. These men typically receive palliative systemic hormonal therapy to control the participants disease. Despite this, over half of men will have cancer progression within 1-2 years and half will die within 5 years.

Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer. First, a subset of patients has oligorecurrent disease, defined as 1-5 sites of metastases. These patients are hypothesized to have an intermediate clinical state in which ablative local therapy with surgery or radiation to all metastatic sites of disease (metastasis-directed therapy; MDT) can lead to durable disease control and potentially cure in select patients. Recent Phase II randomized trials have demonstrated improved long-term progression-free survival with MDT in the absence of systemic therapy.

Yet, 75% of patients receiving MDT for oligorecurrent cancer develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. This is supported by data demonstrating that earlier palliative hormonal therapy is associated with improved survival. In fact, the second approach that has been studied in recent years, is whether escalating hormonal therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves outcomes in men with metastatic prostate cancer. Multiple phase III randomized trials demonstrate that escalating hormonal therapy with these novel therapeutic agents improves progression-free survival and overall survival dramatically. Therefore, these agents have been integrated as an option into today's standard systemic therapy (SST) for metastatic recurrence.

Given the promise of MDT to induce long-term cancer control and the effectiveness of SST to prevent further cancer progression, there is an urgent need to determine whether adding MDT to SST improves disease outcomes further. Additionally, prior studies have excluded patients with local recurrence. However, these comprise a large proportion of Veterans with oligorecurrent prostate cancer.

The primary goal of the investigators study is to determine if adding PET-directed local therapy (treatment of local recurrence on PET/CT and/or MDT) improves disease control compared to SST alone in Veterans with oligorecurrent prostate cancer. The investigators will conduct a multi-institutional phase II/III randomized trial comparing SST with or without PET-directed local therapy. Other goals of the study are to determine any differences in patterns of cancer progression, survival, and quality of life. The investigators also will determine if certain mutations present in tumor DNA can predict if Veterans will benefit from PET-directed local therapy and encourage banking of tumor tissues for future analyses in a separate tumor registry study (VA MAPP).

Details
Condition Malignant neoplasm of prostate, Prostatic disorder, Recurrent Prostate Cancer, Metastatic Prostate Cancer, Prostate Cancer Metastatic, Oligometastasis, prostate carcinoma, prostate cancers, Oligorecurrence
Treatment Degarelix, PET-directed Local Therapy using Surgery, PET-directed Local Therapy using Radiation, Salvage Local Therapy for locally recurrent disease, Goserelin, Histrelin, Leuprolide & Triptorelin, ADT + Nilutamide, Flutamide, & Bicalutamide, ADT + Docetaxel +/- prednisone, ADT + Abiraterone + Prednisone, ADT + Abiraterone + Methylprednisolone, ADT + Apalutamide, ADT + Enzalutamide
Clinical Study IdentifierNCT04787744
SponsorVA Office of Research and Development
Last Modified on21 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 18 years and ECOG performance status 2
Histologically or cytologically confirmed prostate adenocarcinoma
Prior curative-intent local therapy with either upfront definitive radiotherapy (any modality) or prostatectomy +/- post-operative radiotherapy for localized prostate cancer
Any T-classification, Gleason's Grade Group, and pre-treatment PSA at the time of initial curative-intent
treatment are acceptable
Nx, N0, or N1 N-classification at the time of curative-intent local therapy
No metastatic disease at the time of curative-intent local therapy
Rising PSA suspicious for biochemical recurrence after local therapy. In general, this will be defined as
PSA 0.2 ng/ml x 2 after prostatectomy +/- post-operative radiotherapy
Elevation of PSA 2 ng/ml above the nadir after definitive radiotherapy
Two consecutively rising PSAs with evidence of metastasis on the imaging studies described in 5.6
The following lab studies must be performed within 90 days of enrollment (except in patients who have already started SST)
PSA
Total testosterone > 100 ng/dl
The following imaging studies must be performed within 90 days of enrollment (except in patients who have started SST)
CT or MRI abdomen/pelvis
Technetium (Tc99m-MDP) or sodium fluoride (NaF) bone scan (sodium fluoride preferred)
FDA-approved standard of care PET/CT (currently PSMA, Fluciclovine, choline,)
The imaging studies in 6 reveal a total of 1-5 lesions suspicious for nodal recurrence or metastasis from prostate cancer as determined by the official report
Veterans with radiographic evidence of local recurrence: There must be recurrence on imaging in at least one other site in addition to a local recurrence in the prostate, seminal vesicles, or prostate bed. In other words, patients with a local recurrence in the prostate, prostate bed, or seminal vesicles only are not eligible. The Veteran must be a candidate for salvage local therapy
If a Veteran has started SST for this recurrence prior to enrollment, he is eligible if all of the following criteria are met
He has been on SST for 120 days
The imaging studies required for enrollment were performed within 90 days prior to the SST start date. These studies will be entered as the enrollment studies
Biochemically recurrent PSA and serum testosterone > 100 ng/dl within 90 days prior to SST start
There is no evidence of castration-resistant prostate cancer (see section 11.4 for definition of castration-resistant prostate cancer)
No other prior malignancy is allowed except for 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

Exclusion Criteria

Any current or prior evidence of castration-resistant prostate cancer (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)
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 are not eligible
Prior nodal, bone, or visceral metastasis after curative-intent therapy other than those identified on the enrollment imaging studies, whether treated or untreated
Prior local therapy with surgery or radiation to the nodal or distant metastases identified on the enrollment PET/CT
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 or surgeon/urologist
Any other previous or current condition, which, in the judgement of the responsible clinician, is likely to interfere with any STARPORT treatments or assessments
Patients with psychiatric illness/social situations that would limit compliance with study requirements
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