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

January 22, 2024 updated by: VA Office of Research and Development

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

464

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Long Beach, California, United States, 90822
        • Recruiting
        • VA Long Beach Healthcare System, Long Beach, CA
        • Contact:
      • West Los Angeles, California, United States, 90073
        • Recruiting
        • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
        • Contact:
    • Florida
      • Bay Pines, Florida, United States, 33744
        • Recruiting
        • Bay Pines VA Healthcare System, Pay Pines, FL
        • Contact:
    • Illinois
      • Hines, Illinois, United States, 60141-3030
        • Recruiting
        • Edward Hines Jr. VA Hospital, Hines, IL
        • Contact:
        • Principal Investigator:
          • Abhishek Solanki, MD MS
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Recruiting
        • Richard L. Roudebush VA Medical Center, Indianapolis, IN
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Not yet recruiting
        • Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • Recruiting
        • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Recruiting
        • VA Ann Arbor Healthcare System, Ann Arbor, MI
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417-2309
        • Recruiting
        • Minneapolis VA Health Care System, Minneapolis, MN
        • Contact:
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • Recruiting
        • Kansas City VA Medical Center, Kansas City, MO
        • Contact:
    • New Jersey
      • East Orange, New Jersey, United States, 07018
        • Recruiting
        • East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ
        • Contact:
    • New York
      • New York, New York, United States, 10010-5011
        • Recruiting
        • Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Durham VA Medical Center, Durham, NC
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Louis Stokes VA Medical Center, Cleveland, OH
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4551
        • Recruiting
        • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Michael E. DeBakey VA Medical Center, Houston, TX
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Recruiting
        • Hunter Holmes McGuire VA Medical Center, Richmond, VA
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53295-1000
        • Recruiting
        • Clement J. Zablocki VA Medical Center, Milwaukee, WI
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.
    • Technetium (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 FDA-approved standard of care PET/CT (currently PSMA, Fluciclovine, choline) per-formed 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Systemic Therapy (SST)
All Veterans will receive SST (if De novo, Veterans will receive prostate-directed radiation).
Drug: Goserelin, Histrelin, Leuprolide & Triptorelin
Androgen deprivation therapy (ADT) using an LHRH agonist
Drug: ADT + Nilutamide, Flutamide, & Bicalutamide
ADT adding anti-androgen therapy to an LHRH agonist
Drug: Degarelix & Relugolix
ADT using an LHRH Antagonist.
Drug: ADT + Docetaxel +/- prednisone
Enhanced SST using chemohormonal therapy
Drug: ADT + Abiraterone + Prednisone
Enhanced SST using Abiraterone + Prednisone
Drug: ADT + Abiraterone + Methylprednisolone
Enhanced SST using Abiraterone + Methylprednisolone
Drug: ADT + Apalutamide
Enhanced SST using ADT + Apalutamide
Drug: ADT + Enzalutamide
Enhanced SST using ADT + Enzalutamide
Radiation: 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.
Experimental: 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.
Drug: Goserelin, Histrelin, Leuprolide & Triptorelin
Androgen deprivation therapy (ADT) using an LHRH agonist
Drug: ADT + Nilutamide, Flutamide, & Bicalutamide
ADT adding anti-androgen therapy to an LHRH agonist
Drug: Degarelix & Relugolix
ADT using an LHRH Antagonist.
Drug: ADT + Docetaxel +/- prednisone
Enhanced SST using chemohormonal therapy
Drug: ADT + Abiraterone + Prednisone
Enhanced SST using Abiraterone + Prednisone
Drug: ADT + Abiraterone + Methylprednisolone
Enhanced SST using Abiraterone + Methylprednisolone
Drug: ADT + Apalutamide
Enhanced SST using ADT + Apalutamide
Drug: ADT + Enzalutamide
Enhanced SST using ADT + Enzalutamide
Procedure: PET-directed Local Therapy using Surgery
Surgery will be used to treat metastases.
Radiation: 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.

Other: 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.
Radiation: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Castration-resistant prostate cancer-free survival (CRPC-free survival)
Time Frame: 4 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic progression-free survival (rPFS)
Time Frame: 4 years
rPFS is a time-to-event outcome defined as the length of time from randomization to radiographic progression of prostate cancer or death.
4 years
Clinical progression-free survival (cPFS)
Time Frame: 4 years
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.
4 years
Freedom from index lesion progression (FFILP)
Time Frame: 4 years
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.
4 years
New metastasis-free survival (MFS)
Time Frame: 4 years
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.
4 years
Prostate cancer-specific survival (PCSS)
Time Frame: 4 years
PCSS is a time-to-event outcome defined as the length of time from randomization to death from prostate cancer.
4 years
Overall survival (OS)
Time Frame: 4 years
OS is a time-to-event outcome defined as the length of time from randomization to death from any cause.
4 years
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity
Time Frame: 4 years
Toxicities will be evaluated based on system organ class and a higher number in the grading system is reflective of more severe toxicity.
4 years
Patient-reported quality of life measured by the EORTC QLQ-C30 3.0
Time Frame: 2 years
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.
2 years
Expanded Prostate cancer Index Composite Short Form (EPIC-26)
Time Frame: 2 years
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.
2 years
Patient-reported health-related quality of life measured by the EQ5D-5L
Time Frame: 2 years
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."
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Abhishek Solanki, MD MS, Edward Hines Jr. VA Hospital, Hines, IL

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

February 25, 2021

First Submitted That Met QC Criteria

March 4, 2021

First Posted (Actual)

March 9, 2021

Study Record Updates

Last Update Posted (Actual)

January 24, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONCA-026-20S
  • CX002277-01 (Other Grant/Funding Number: VA Clinical Science Research & Development)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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