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

NCT04787744 | Recruiting Phase 2 DMC

• 2 other identifiers: ONCA-026-20SCX002277-01
• Study Type: interventional
• Target: 464
• Locations: 1 country
• Sites: 20

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Castration-resistant prostate cancer-free survival (CRPC-free survival)

  CRPC-free survival is a time-to-event outcome defined as the length of time from randomization to the first occurrence of failure. The following are forms of failure in the setting of a castrate testosterone level: PSA progression, radiographic progression, symptomatic skeletal event due to progression, and death.

  4 years

Secondary Outcomes (10)

• Radiographic progression-free survival (rPFS)

  4 years

• Clinical progression-free survival (cPFS)

  4 years

• Freedom from index lesion progression (FFILP)

  4 years

• New metastasis-free survival (MFS)

  4 years

• Prostate cancer-specific survival (PCSS)

  4 years

Study Arms (2)

Standard Systemic Therapy (SST)

ACTIVE COMPARATOR

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

Drug: Goserelin, Histrelin, Leuprolide & Triptorelin; Drug: ADT + Nilutamide, Flutamide, & Bicalutamide; Drug: Degarelix & Relugolix; Drug: ADT + Docetaxel +/- prednisone; Drug: ADT + Abiraterone + Prednisone; Drug: ADT + Abiraterone + Methylprednisolone; Drug: ADT + Apalutamide; Drug: ADT + Enzalutamide; Radiation: Prostate-directed Radiation for De novo oligometastatic prostate cancer

SST + PET-directed local therapy

EXPERIMENTAL

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.

Procedure: PET-directed Local Therapy using Surgery; Radiation: PET-directed Local Therapy using Radiation; Other: Salvage Local Therapy for locally recurrent disease; Drug: Goserelin, Histrelin, Leuprolide & Triptorelin; Drug: ADT + Nilutamide, Flutamide, & Bicalutamide; Drug: Degarelix & Relugolix; Drug: ADT + Docetaxel +/- prednisone; Drug: ADT + Abiraterone + Prednisone; Drug: ADT + Abiraterone + Methylprednisolone; Drug: ADT + Apalutamide; Drug: ADT + Enzalutamide; Radiation: Prostate-directed Radiation for De novo oligometastatic prostate cancer

Interventions

PET-directed Local Therapy using Surgery PROCEDURE

Surgery will be used to treat metastases.

SST + PET-directed local therapy

PET-directed Local Therapy using Radiation 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.

SST + PET-directed local therapy

Salvage Local Therapy for locally recurrent disease 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.

SST + PET-directed local therapy

Goserelin, Histrelin, Leuprolide & Triptorelin DRUG

Androgen deprivation therapy (ADT) using an LHRH agonist

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

ADT + Nilutamide, Flutamide, & Bicalutamide DRUG

ADT adding anti-androgen therapy to an LHRH agonist

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

Degarelix & Relugolix DRUG

ADT using an LHRH Antagonist.

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

ADT + Abiraterone + Prednisone DRUG

Enhanced SST using Abiraterone + Prednisone

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

ADT + Abiraterone + Methylprednisolone DRUG

Enhanced SST using Abiraterone + Methylprednisolone

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

ADT + Apalutamide DRUG

Enhanced SST using ADT + Apalutamide

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

ADT + Enzalutamide DRUG

Enhanced SST using ADT + Enzalutamide

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

Prostate-directed Radiation for De novo oligometastatic prostate cancer 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; Standard Systemic Therapy (SST)

ADT + Docetaxel +/- prednisone DRUG

Enhanced SST using chemohormonal therapy

SST + PET-directed local therapy; Standard Systemic Therapy (SST)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male with prostate cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (20)

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

RECRUITING

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

West Los Angeles, California, 90073, United States

RECRUITING

Washington DC VA Medical Center, Washington, DC

Washington D.C., District of Columbia, 20422-0001, United States

RECRUITING

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, 33744, United States

RECRUITING

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-3030, United States

RECRUITING

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

RECRUITING

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

Baltimore, Maryland, 21201, United States

RECRUITING

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

Boston, Massachusetts, 02130, United States

RECRUITING

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

ACTIVE NOT RECRUITING

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, 64128-2226, United States

TERMINATED

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

East Orange, New Jersey, 07018, United States

TERMINATED

VA NY Harbor Healthcare System, New York, NY

New York, New York, 10010-5011, United States

TERMINATED

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705, United States

RECRUITING

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

RECRUITING

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

Philadelphia, Pennsylvania, 19104-4551, United States

RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

RECRUITING

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249, United States

RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

RECRUITING

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, 53295-1000, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Goserelin; histrelin; Leuprolide; Triptorelin Pamoate; Androgen Antagonists; nilutamide; Flutamide; bicalutamide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; relugolix; abiraterone; Prednisone; Methylprednisolone; apalutamide; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Study Officials

• Abhishek Solanki, MD MS

  Edward Hines Jr. VA Hospital, Hines, IL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abhishek Solanki, MD MS

CONTACT

(708) 202-8387; Abhishek.Solanki@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 9, 2021
• Study Start: July 1, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): March 30, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)