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

NCT ID: NCT04787744

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 464 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-01
• Study Completion Date: 2029-03-30

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.

Conditions

Prostate Cancer; Oligometastasis; Oligorecurrence; Recurrent Prostate Cancer; Metastatic Prostate Cancer; De Novo Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Systemic Therapy (SST)

All Veterans will receive SST (if De novo, Veterans will receive prostate-directed radiation).

Group Type: ACTIVE_COMPARATOR

Goserelin, Histrelin, Leuprolide & Triptorelin

Intervention Type: DRUG

Androgen deprivation therapy (ADT) using an LHRH agonist

ADT + Nilutamide, Flutamide, & Bicalutamide

Intervention Type: DRUG

ADT adding anti-androgen therapy to an LHRH agonist

Degarelix & Relugolix

Intervention Type: DRUG

ADT using an LHRH Antagonist.

ADT + Docetaxel +/- prednisone

Intervention Type: DRUG

Enhanced SST using chemohormonal therapy

ADT + Abiraterone + Prednisone

Intervention Type: DRUG

Enhanced SST using Abiraterone + Prednisone

ADT + Abiraterone + Methylprednisolone

Intervention Type: DRUG

Enhanced SST using Abiraterone + Methylprednisolone

ADT + Apalutamide

Intervention Type: DRUG

Enhanced SST using ADT + Apalutamide

ADT + Enzalutamide

Intervention Type: DRUG

Enhanced SST using ADT + Enzalutamide

Prostate-directed Radiation for De novo oligometastatic prostate cancer

Intervention Type: RADIATION

Veterans in ARM 1 will receive prostate-directed RT only and NO treatment to any nodal or distant metastatic sites.

Acceptable dose/fractionations include 55 Gy in 20 fractions and 36 Gy in 6 fractions.

Veterans in ARM 2 should receive prostate-directed local therapy using radiotherapy or radical prostatectomy in addition to PET-directed local therapy to metastases.

SST + PET-directed local therapy

In addition to SST, all Veterans will receive PET-directed local therapy to all metastases using surgery or radiation. If De novo, Veterans will also receive prostate-directed radiation or radical prostatectomy to treat the prostate/prostate bed. The best course of treatment will be determined using shared decision-making between the physician and Veteran.

Group Type: EXPERIMENTAL

PET-directed Local Therapy using Surgery

Intervention Type: PROCEDURE

Surgery will be used to treat metastases.

PET-directed Local Therapy using Radiation

Intervention Type: RADIATION

Radiation therapy will be used to treat metastases.

Radiation options include:

1. Stereotactic body radiotherapy (SBRT) using 1-10 fractions

2. Conventionally fractionated radiotherapy using elective nodal radiotherapy and a simultaneous integrated boost to involved nodes

The selection of the form of metastasis-directed radiotherapy for each metastasis will be determined using shared decision-making between the treating physician and the Veteran.

Salvage Local Therapy for locally recurrent disease

Intervention Type: OTHER

For Veterans who have a local recurrence in addition to oligorecurrent metastatic lesions, they will undergo salvage local therapy using brachytherapy, SBRT, surgery, cryotherapy or HIFU. The selection of modality of salvage local therapy will be determined using shared decision-making between the treating physician and Veteran.

Goserelin, Histrelin, Leuprolide & Triptorelin

Intervention Type: DRUG

Androgen deprivation therapy (ADT) using an LHRH agonist

ADT + Nilutamide, Flutamide, & Bicalutamide

Intervention Type: DRUG

ADT adding anti-androgen therapy to an LHRH agonist

Degarelix & Relugolix

Intervention Type: DRUG

ADT using an LHRH Antagonist.

ADT + Docetaxel +/- prednisone

Intervention Type: DRUG

Enhanced SST using chemohormonal therapy

ADT + Abiraterone + Prednisone

Intervention Type: DRUG

Enhanced SST using Abiraterone + Prednisone

ADT + Abiraterone + Methylprednisolone

Intervention Type: DRUG

Enhanced SST using Abiraterone + Methylprednisolone

ADT + Apalutamide

Intervention Type: DRUG

Enhanced SST using ADT + Apalutamide

ADT + Enzalutamide

Intervention Type: DRUG

Enhanced SST using ADT + Enzalutamide

Prostate-directed Radiation for De novo oligometastatic prostate cancer

Intervention Type: RADIATION

Veterans in ARM 1 will receive prostate-directed RT only and NO treatment to any nodal or distant metastatic sites.

Acceptable dose/fractionations include 55 Gy in 20 fractions and 36 Gy in 6 fractions.

Veterans in ARM 2 should receive prostate-directed local therapy using radiotherapy or radical prostatectomy in addition to PET-directed local therapy to metastases.

Interventions

PET-directed Local Therapy using Surgery

Surgery will be used to treat metastases.

Intervention Type: PROCEDURE

PET-directed Local Therapy using Radiation

Radiation therapy will be used to treat metastases.

Radiation options include:

1. Stereotactic body radiotherapy (SBRT) using 1-10 fractions

2. Conventionally fractionated radiotherapy using elective nodal radiotherapy and a simultaneous integrated boost to involved nodes

The selection of the form of metastasis-directed radiotherapy for each metastasis will be determined using shared decision-making between the treating physician and the Veteran.

Intervention Type: RADIATION

Salvage Local Therapy for locally recurrent disease

For Veterans who have a local recurrence in addition to oligorecurrent metastatic lesions, they will undergo salvage local therapy using brachytherapy, SBRT, surgery, cryotherapy or HIFU. The selection of modality of salvage local therapy will be determined using shared decision-making between the treating physician and Veteran.

Intervention Type: OTHER

Goserelin, Histrelin, Leuprolide & Triptorelin

Androgen deprivation therapy (ADT) using an LHRH agonist

Intervention Type: DRUG

ADT + Nilutamide, Flutamide, & Bicalutamide

ADT adding anti-androgen therapy to an LHRH agonist

Intervention Type: DRUG

Degarelix & Relugolix

ADT using an LHRH Antagonist.

Intervention Type: DRUG

ADT + Docetaxel +/- prednisone

Enhanced SST using chemohormonal therapy

Intervention Type: DRUG

ADT + Abiraterone + Prednisone

Enhanced SST using Abiraterone + Prednisone

Intervention Type: DRUG

ADT + Abiraterone + Methylprednisolone

Enhanced SST using Abiraterone + Methylprednisolone

Intervention Type: DRUG

ADT + Apalutamide

Enhanced SST using ADT + Apalutamide

Intervention Type: DRUG

ADT + Enzalutamide

Enhanced SST using ADT + Enzalutamide

Intervention Type: DRUG

Prostate-directed Radiation for De novo oligometastatic prostate cancer

Veterans in ARM 1 will receive prostate-directed RT only and NO treatment to any nodal or distant metastatic sites.

Acceptable dose/fractionations include 55 Gy in 20 fractions and 36 Gy in 6 fractions.

Veterans in ARM 2 should receive prostate-directed local therapy using radiotherapy or radical prostatectomy in addition to PET-directed local therapy to metastases.

Intervention Type: RADIATION

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abhishek Solanki, MD MS

Role: PRINCIPAL_INVESTIGATOR

Edward Hines Jr. VA Hospital, Hines, IL

Locations

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status: RECRUITING

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Site Status: RECRUITING

Washington DC VA Medical Center, Washington, DC

Washington D.C., District of Columbia, United States

Site Status: RECRUITING

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, United States

Site Status: RECRUITING

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, United States

Site Status: RECRUITING

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, United States

Site Status: RECRUITING

Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Baltimore, Maryland, United States

Site Status: RECRUITING

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

Site Status: RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Site Status: ACTIVE_NOT_RECRUITING

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, United States

Site Status: TERMINATED

East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ

East Orange, New Jersey, United States

Site Status: TERMINATED

VA NY Harbor Healthcare System, New York, NY

New York, New York, United States

Site Status: TERMINATED

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

Site Status: RECRUITING

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Site Status: RECRUITING

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Site Status: RECRUITING

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, United States

Site Status: RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, United States

Site Status: RECRUITING

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Abhishek Solanki, MD MS

Role: CONTACT

Abhishek.Solanki@va.gov

(708) 202-8387 ext. 27091

Facility Contacts

Robert Kwon, MD

Role: primary

Robert.Kwon1@va.gov

562-826-5606

Nicholas Nickols, MD

Role: primary

nicholas.nickols@va.gov

310-478-3711 ext. 44127

Ruchika Gutt, MD

Role: primary

ruchika.gutt@va.gov

301-928-0873

Robert Curran, BA

Role: backup

robert.curran@va.gov

202.745.2277

Ryan Burri, MD

Role: primary

ryan.burri@va.gov

727-398-6661 ext. 13912

Abhishek Solanki, MD MS

Role: primary

Abhishek.Solanki@va.gov

708-202-8387 ext. 27091

Ronald Shapiro, MD

Role: primary

ronald.shapiro@va.gov

317-988-3652

Christine Bang, MD

Role: primary

Christine.Bang@va.gov

Sonny Batra, MD

Role: primary

Sonny.Batra@va.gov

857-404-1215

David Elliot, MD

Role: primary

david.elliott1@va.gov

734-845-3914

Rhonda Bitting, MD

Role: primary

rhonda.bitting@va.gov

415-516-8256

Aryavarta Kumar, MD

Role: primary

aryavarta.kumar@va.gov

216-536-1201

Yu-Ning Wong, MD

Role: primary

Yu-Ning.Wong@va.gov

215-823-5900

Albert Chen, MD

Role: primary

albert.chen3@va.gov

713-794-7190

Hann-Hsiang Chao, MD

Role: primary

hann-hsiang.chao@va.gov

804-675-5000 ext. 3750

Jessica Schuster, MD

Role: primary

Jessica.Schuster@va.gov

608-256-1901 ext. 11097

Leigh Fisher

Role: backup

Leigh.Fisher@va.gov

6082561901 ext. 10313

Lindsay Puckett, MD

Role: primary

Lindsay.Puckett@va.gov

414-384-2000 ext. 42590

Other Identifiers

CX002277-01

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ONCA-026-20S

Identifier Type: -

Identifier Source: org_study_id