Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease

Neil R Parikh, Claudia Huiza, Jill S Patel, Sonny Tsai, Nathisha Kalpage, May Thein, Sage Pitcher, Steve P Lee, Warren S Inouye, Mark L Jordan, Homayoon Sanati, Lida Jafari, Carol J Bennett, Greg E Gin, Amar U Kishan, Robert E Reiter, Michael Lewis, Ahmad Sadeghi, William J Aronson, Isla P Garraway, Matthew B Rettig, Nicholas G Nickols, Neil R Parikh, Claudia Huiza, Jill S Patel, Sonny Tsai, Nathisha Kalpage, May Thein, Sage Pitcher, Steve P Lee, Warren S Inouye, Mark L Jordan, Homayoon Sanati, Lida Jafari, Carol J Bennett, Greg E Gin, Amar U Kishan, Robert E Reiter, Michael Lewis, Ahmad Sadeghi, William J Aronson, Isla P Garraway, Matthew B Rettig, Nicholas G Nickols

Abstract

Background: The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy.

Methods: Patients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1-5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of < 0.05 ng/mL six months after recovery of serum testosterone ≥150 ng/dL. Secondary endpoints include time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability.

Discussion: To our knowledge, this is the first trial that tests a comprehensive systemic and tumor directed therapeutic strategy for patients with newly diagnosed oligometastatic prostate cancer. This trial, and others like it, represent the critical first step towards curative intent therapy for a patient population where palliation has been the norm.

Trial registration: Clinicaltrials.gov identifier: NCT03298087 (registration date: September 29, 2017).

Keywords: Abiraterone; Androgen deprivation therapy; Apalutamide; Leuprolide; Metastasis-directed therapy; Oligometastases; Prostate cancer; Radical prostatectomy; Stereotactic body radiotherapy.

Conflict of interest statement

Ethics approval and consent to participate

The study is approved by the IRBs of VA Greater Los Angeles and VA Long Beach Healthcare Systems and is registered on clinicaltrials.gov (NCT03298087). IRB reference number PCC:2017–040371. Subjects consent to participate after thorough discussion by signing of the IRB approved informed consent document.

Consent for publication

This manuscript does not include details, images, or videos relating to an individual person.

Competing interests

The authors declare that they have no competing interests. Full disclosures for P.I. NN include: research support from Janssen, Varian, and Bayer; stock options with GSI Inc. and ROAR; and consulting with GSI Inc.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

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Fig. 1
Trial Schema

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