Clinical trial NCT04787744: Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer
Official title: Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for OligoRecurrenT Prostate Cancer (VA STARPORT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Prostate Cancer
Oligometastasis
Oligorecurrence
Recurrent Prostate Cancer
Metastatic Prostate Cancer
De Novo Prostate Cancer
Keywords: Prostate Cancer
Metastasis
Oligorecurrence
PET-directed local therapy
Standard Systemic Therapy
SBRT
Oligometastasis
Oligorecurrent
Metastasis-directed therapy
Salvage Local Therapy
Recurrent Prostate Cancer
Fluciclovine
PSMA
Choline
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2021-03-09
Enrollment: 464
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 their 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 oligometastatic disease. 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 oligometastatic 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 prostate cancer.

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 recurrent oligometastatic prostate cancer. The primary goal of our study is to determine if adding PET-directed local therapy (MDT and treatment of primary tumor \[de novo\] or primary tumor local recurrence on PET/CT if applicable) improves disease control compared to SST alone in Veterans with oligometastatic prostate cancer. This is 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. We also will determine if certain mutations present in tumor DNA can predict if Veterans will benefit from PET-directed local therapy.

Eligibility criteria: 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.

Primary outcomes:
measure: Castration-resistant prostate cancer-free survival (CRPC-free survival)
timeFrame: 4 years
Secondary outcomes:
measure: Radiographic progression-free survival (rPFS)
timeFrame: 4 years
measure: Clinical progression-free survival (cPFS)
timeFrame: 4 years
measure: Freedom from index lesion progression (FFILP)
timeFrame: 4 years
measure: New metastasis-free survival (MFS)
timeFrame: 4 years
measure: Prostate cancer-specific survival (PCSS)
timeFrame: 4 years
measure: Overall survival (OS)
timeFrame: 4 years
measure: Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity
timeFrame: 4 years
measure: Patient-reported quality of life measured by the EORTC QLQ-C30 3.0
timeFrame: 2 years
measure: Expanded Prostate cancer Index Composite Short Form (EPIC-26)
timeFrame: 2 years
measure: Patient-reported health-related quality of life measured by the EQ5D-5L
timeFrame: 2 years
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System, Pay Pines, FL
state: Florida
city: Hines
country: United States
facility: Edward Hines Jr. VA Hospital, Hines, IL
state: Illinois
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center, Indianapolis, IN
state: Indiana
city: Baltimore
country: United States
facility: Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
state: Maryland
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City VA Medical Center, Kansas City, MO
state: Missouri
city: East Orange
country: United States
facility: East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ
state: New Jersey
city: New York
country: United States
facility: Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
state: New York
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
city: Cleveland
country: United States
facility: Louis Stokes VA Medical Center, Cleveland, OH
state: Ohio
city: Philadelphia
country: United States
facility: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
state: Pennsylvania
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center, Richmond, VA
state: Virginia
city: Madison
country: United States
facility: William S. Middleton Memorial Veterans Hospital, Madison, WI
state: Wisconsin
city: Milwaukee
country: United States
facility: Clement J. Zablocki VA Medical Center, Milwaukee, WI
state: Wisconsin
Study officials:
affiliation: Edward Hines Jr. VA Hospital, Hines, IL
name: Abhishek Solanki, MD MS
role: PRINCIPAL_INVESTIGATOR
References: