Trials / Recruiting
RecruitingNCT04787744
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer
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)
- Status
- Recruiting
- Phase
- Phase 2 / Phase 3
- Study type
- Interventional
- Enrollment
- 464 (estimated)
- Sponsor
- VA Office of Research and Development · Federal
- Sex
- Male
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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
Interventions
| Type | Name | Description |
|---|---|---|
| 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. |
| 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. |
Timeline
- Start date
- 2021-07-01
- Primary completion
- 2026-09-30
- Completion
- 2029-03-30
- First posted
- 2021-03-09
- Last updated
- 2026-04-08
Locations
20 sites across 1 country: United States
Source: ClinicalTrials.gov record NCT04787744. Inclusion in this directory is not an endorsement.