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

NCT04787744

Description:

The primary goal of this study is to determine if adding PET-directed local therapy improves disease control compared to standard systemic therapy alone in Veterans with oligorecurrent prostate cancer on PET/CT. The investigators will conduct a multi-institutional phase II/III randomized trial comparing SST with or without PET-directed local therapy using radiation or surgery to all metastases and if a local recurrence is present.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for OligoRecurrenT 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)

Clinical Trial IDs

  • ORG STUDY ID: ONCA-026-20S
  • SECONDARY ID: CX002277-01
  • NCT ID: NCT04787744

Conditions

  • Prostate Cancer
  • Oligometastasis
  • Oligorecurrence
  • Recurrent Prostate Cancer
  • Metastatic Prostate Cancer

Interventions

DrugSynonymsArms
Goserelin, Histrelin, Leuprolide & TriptorelinSST + PET-directed local therapy
ADT + Nilutamide, Flutamide, & BicalutamideSST + PET-directed local therapy
DegarelixSST + PET-directed local therapy
ADT + Docetaxel +/- prednisoneSST + PET-directed local therapy
ADT + Abiraterone + PrednisoneSST + PET-directed local therapy
ADT + Abiraterone + MethylprednisoloneSST + PET-directed local therapy
ADT + ApalutamideSST + PET-directed local therapy
ADT + EnzalutamideSST + PET-directed local therapy

Purpose

The primary goal of this study is to determine if adding PET-directed local therapy improves disease control compared to standard systemic therapy alone in Veterans with oligorecurrent prostate cancer on PET/CT. The investigators will conduct a multi-institutional phase II/III randomized trial comparing SST with or without PET-directed local therapy using radiation or surgery to all metastases and if a local recurrence is present.

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 the participants 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 oligorecurrent disease,
      defined as 1-5 sites of metastases. 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 oligorecurrent 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 recurrence.

      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
      oligorecurrent prostate cancer.

      The primary goal of the investigators study is to determine if adding PET-directed local
      therapy (treatment of local recurrence on PET/CT and/or MDT) improves disease control
      compared to SST alone in Veterans with oligorecurrent prostate cancer. The investigators will
      conduct 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. The investigators also will
      determine if certain mutations present in tumor DNA can predict if Veterans will benefit from
      PET-directed local therapy and encourage banking of tumor tissues for future analyses in a
      separate tumor registry study (VA MAPP).
    

Trial Arms

NameTypeDescriptionInterventions
Standard Systemic Therapy (SST)Active ComparatorAll Veterans will receive SST
  • Goserelin, Histrelin, Leuprolide & Triptorelin
  • ADT + Nilutamide, Flutamide, & Bicalutamide
  • Degarelix
  • ADT + Docetaxel +/- prednisone
  • ADT + Abiraterone + Prednisone
  • ADT + Abiraterone + Methylprednisolone
  • ADT + Apalutamide
  • ADT + Enzalutamide
SST + PET-directed local therapyExperimentalIn addition to SST, all Veterans will receive PET-directed local therapy to all metastases using surgery or radiation. The selection of surgery or radiation to each metastasis will be determined using shared decision-making between the physician and Veteran. For Veterans with a local recurrence, this will be treated with salvage local therapy.
  • Goserelin, Histrelin, Leuprolide & Triptorelin
  • ADT + Nilutamide, Flutamide, & Bicalutamide
  • Degarelix
  • ADT + Docetaxel +/- prednisone
  • ADT + Abiraterone + Prednisone
  • ADT + Abiraterone + Methylprednisolone
  • ADT + Apalutamide
  • ADT + Enzalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Age 18 years and ECOG performance status 2.

          -  Histologically or cytologically confirmed prostate adenocarcinoma.

          -  Prior curative-intent local therapy with either upfront definitive radiotherapy (any
             modality) or prostatectomy +/- post-operative radiotherapy for localized prostate
             cancer

               -  Any T-classification, Gleason's Grade Group, and pre-treatment PSA at the time of
                  initial curative-intent

               -  treatment are acceptable.

               -  Nx, N0, or N1 N-classification at the time of curative-intent local therapy

               -  No metastatic disease at the time of curative-intent local therapy

          -  Rising PSA suspicious for biochemical recurrence after local therapy. In general, this
             will be defined as:

               -  PSA 0.2 ng/ml x 2 after prostatectomy +/- post-operative radiotherapy

               -  Elevation of PSA 2 ng/ml above the nadir after definitive radiotherapy

               -  Two consecutively rising PSAs with evidence of metastasis on the imaging studies
                  described in 5.6

          -  The following lab studies must be performed within 90 days of enrollment (except in
             patients who have already started SST):

               -  PSA

               -  Total testosterone > 100 ng/dl

          -  The following imaging studies must be performed within 90 days of enrollment (except
             in patients who have started SST):

               -  CT or MRI abdomen/pelvis

               -  Technetium (Tc99m-MDP) or sodium fluoride (NaF) bone scan (sodium fluoride
                  preferred)

               -  FDA-approved standard of care PET/CT (currently PSMA, Fluciclovine, choline,)

          -  The imaging studies in 6 reveal a total of 1-5 lesions suspicious for nodal recurrence
             or metastasis from prostate cancer as determined by the official report.

          -  Veterans with radiographic evidence of local recurrence: There must be recurrence on
             imaging in at least one other site in addition to a local recurrence in the prostate,
             seminal vesicles, or prostate bed. In other words, patients with a local recurrence in
             the prostate, prostate bed, or seminal vesicles only are not eligible. The Veteran
             must be a candidate for salvage local therapy.

          -  If a Veteran has started SST for this recurrence prior to enrollment, he is eligible
             if all of the following criteria are met:

               -  He has been on SST for 120 days.

               -  The imaging studies required for enrollment were performed within 90 days prior
                  to the SST start date. These studies will be entered as the enrollment studies.

               -  Biochemically recurrent PSA and serum testosterone > 100 ng/dl within 90 days
                  prior to SST start.

               -  There is no evidence of castration-resistant prostate cancer (see section 11.4
                  for definition of castration-resistant prostate cancer)

          -  No other prior malignancy is allowed except for 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.

        Exclusion Criteria:

          -  Any current or prior evidence of castration-resistant prostate cancer (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).

          -  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 are not eligible.

          -  Prior nodal, bone, or visceral metastasis after curative-intent therapy other than
             those identified on the enrollment imaging studies, whether treated or untreated.

          -  Prior local therapy with surgery or radiation to the nodal or distant metastases
             identified on the enrollment PET/CT.

          -  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 or
             surgeon/urologist.

          -  Any other previous or current condition, which, in the judgement of the responsible
             clinician, is likely to interfere with any STARPORT treatments or assessments.

          -  Patients with psychiatric illness/social situations that would limit compliance with
             study requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Castration-resistant prostate cancer-free survival (CRPC-free survival)
Time Frame:4 years
Safety Issue:
Description: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.

Secondary Outcome Measures

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

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:VA Office of Research and Development

Trial 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

Last Updated

July 13, 2021