Prostate CancerPhase 2/3VA STARPORTNCT04787744
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer
A Phase 2/3 study testing PET-directed Local Therapy using Surgery, PET-directed Local Therapy using Radiation and Salvage Local Therapy for locally recurrent disease in people with Prostate Cancer and Oligometastasis, run by VA Office of Research and Development at 20 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Oligometastasis, Oligorecurrence
- What is being tested?
- PET-directed Local Therapy using Surgery, PET-directed Local Therapy using Radiation and Salvage Local Therapy for locally recurrent disease
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 378 participants
- Where
- 20 sitesUnited States
- Study dates
- 1 Jul 2021to 30 Mar 2029
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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, prostate-specific antigen (PSA) suspicious for biochemical recurrence after local therapy, with lab value(s) taken prior to start of standard systemic therapy (SST), if current standard systemic therapy has already started, or within 90 days prior to enrollment if not already on standard systemic therapy, and meeting one of the three below categories:
- Prostate-specific antigen (PSA) 0.2 nanograms per milliliter (ng/ml) x 2 after prostatectomy +/- post-operative radiotherapy; Elevation of prostate-specific antigen 2 nanograms per deciliter (ng/dl) 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 standard systemic therapy agents for prostate cancer, a total testosterone 100 nanograms per deciliter (ng/dl) after completion of the prior episode of standard systemic therapy and before the start of current standard systemic therapy or within 30 days of starting current standard systemic therapy if the patient has already started standard systemic therapy for recurrence.
- For patients who have no prior history of an episode of therapy with standard systemic therapy agents and have already started standard systemic therapy for recurrence, this pre-standard systemic therapy testosterone is not required.
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- Computed tomography (CT) or magnetic resonance imaging (MRI) abdomen/pelvis performed prior to start of standard systemic therapy (if current standard systemic therapy has already started) or within 90 days prior to enrollment if not already on standard systemic therapy. 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/CTstandard systemic therapy Yechnetium (Tc99m-MDP) or sodium fluoride (NaF) bone scan (sodium fluoride preferred) performed prior to start of standard systemic therapy (if current standard systemic therapy has already started), or within 90 days prior to enrollment if not already on standard systemic therapy. This is optional for patients who have a PSMA PET/CT. Prostate PET/CT (currently PSMA, Fluciclovine, choline) performed prior to start of standard systemic therapy (if current standard systemic therapy has already started), or within 90 days prior to enrollment if not already on standard systemic therapy.
- 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 standard systemic therapy at the time of enrollment only:
- Has been on standard systemic therapy 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
Who cannot join
- Any current or prior evidence of castration-resistant prostate cancer, defined as two consecutive rises in serum prostate-specific antigen (PSA), obtained at a minimum of 1-week interval, with the final PSA value >/= 1 nanograms per milliliter, while having a total testosterone < 50 nanograms per deciliter)
- 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
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- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105
Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
Baltimore, Maryland, 21201
Bay Pines VA Healthcare System, Pay Pines, FL
Bay Pines, Florida, 33744
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705
East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ
East Orange, New Jersey, 07018
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-3030
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030
Richard L. Roudebush VA Medical Center, Indianapolis, IN
Indianapolis, Indiana, 46202-2884
Kansas City VA Medical Center, Kansas City, MO
Kansas City, Missouri, 64128-2226
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, 90822
William S. Middleton Memorial Veterans Hospital, Madison, WI
Madison, Wisconsin, 53705-2254
Clement J. Zablocki VA Medical Center, Milwaukee, WI
Milwaukee, Wisconsin, 53295-1000
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309
VA NY Harbor Healthcare System, New York, NY
New York, New York, 10010-5011
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19104-4551
Hunter Holmes McGuire VA Medical Center, Richmond, VA
Richmond, Virginia, 23249
Washington DC VA Medical Center, Washington, DC
Washington D.C., District of Columbia, 20422-0001
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
West Los Angeles, California, 90073
About this study
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)
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.
Read the 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
- Being tested
- 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
- 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
- Medical subject headings
- Prostatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET-directed Local Therapy using SurgeryProcedure or surgery
Surgery will be used to treat metastases.
PET-directed Local Therapy using RadiationRadiation
Radiation therapy will be used to treat metastases.
Radiation options include:
- Stereotactic body radiotherapy (SBRT) using 1-10 fractions
- 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 diseaseOther
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 & TriptorelinDrug
Androgen deprivation therapy (ADT) using an LHRH agonist
ADT + Nilutamide, Flutamide, & BicalutamideDrug
ADT adding anti-androgen therapy to an LHRH agonist
Degarelix & RelugolixDrug
ADT using an LHRH Antagonist.
ADT + Docetaxel +/- prednisoneDrug
Enhanced SST using chemohormonal therapy
ADT + Abiraterone + PrednisoneDrug
Enhanced SST using Abiraterone + Prednisone
ADT + Abiraterone + MethylprednisoloneDrug
Enhanced SST using Abiraterone + Methylprednisolone
ADT + ApalutamideDrug
Enhanced SST using ADT + Apalutamide
ADT + EnzalutamideDrug
Enhanced SST using ADT + Enzalutamide
Prostate-directed Radiation for De novo oligometastatic prostate cancerRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard Systemic Therapy (SST) | Active comparator | All Veterans will receive SST (if De novo, Veterans will receive prostate-directed radiation). Receives: 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 years
Secondary outcomes (10)
Radiographic progression-free survival (rPFS)
rPFS is a time-to-event outcome defined as the length of time from randomization to radiographic progression of prostate cancer or death.
Measured: 4 years
Clinical progression-free survival (cPFS)
cPFS is a time-to-event outcome defined as the length of time from randomization to radiographic progression on conventional imaging, symptomatic skeletal event due to progression, or death.
Measured: 4 years
Freedom from index lesion progression (FFILP)
FFILP is a time-to-event outcome defined as the length of time from randomization to progression of any of the enrollment index oligorecurrent lesions.
Measured: 4 years
New metastasis-free survival (MFS)
New MFS is a time-to-event outcome (MFS) defined as the length of time from randomization to the development of a new metastasis that was not present at the time of enrollment, or death.
Measured: 4 years
Prostate cancer-specific survival (PCSS)
PCSS is a time-to-event outcome defined as the length of time from randomization to death from prostate cancer.
Measured: 4 years
Overall survival (OS)
OS is a time-to-event outcome defined as the length of time from randomization to death from any cause.
Measured: 4 years
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity
Toxicities will be evaluated based on system organ class and a higher number in the grading system is reflective of more severe toxicity.
Measured: 4 years
Patient-reported quality of life measured by the EORTC QLQ-C30 3.0
The QLQ-C30 is composed of 30 items. These include five functional scales, three symptom scales, a global health status/QoL scale, and six single items. Raw scores will be converted to standardized scores ranging from 0 to 100. A higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms.
Measured: 2 years
Expanded Prostate cancer Index Composite Short Form (EPIC-26)
EPIC-26 contains 26 items in 5 domains (Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal). Raw scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
Measured: 2 years
Patient-reported health-related quality of life measured by the EQ5D-5L
EQ5D-5l consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each dimension has 5 levels. The digits for the 5 dimensions is combined to describe the health state (higher total reflect a higher health state). There is also a vertical visual analogue scale to be used as a quantitative measure that reflects the patient's own judgement with the endpoints labelled as "The best health you can imagine" and "The worst health you can imagine."
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start1 Jul 2021
- Primary completion2 Oct 2026
- Study completion30 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 378 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Abhishek Solanki, MD MS, Principal investigator, Edward Hines Jr. VA Hospital, Hines, IL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04787744
- Sponsor's protocol ID
- ONCA-026-20S
- Other IDs
- 1I01CX002277-01, CX002277-01
- Acronym
- VA STARPORT
- Status last verified
- Oct 2026
- First submitted
- 25 Feb 2021
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No