Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer

Benjamin A Gartrell,Howard I Scher,Avi Retter,Mack Roach,Gerald H Sokol,Giuseppe Del Priore

doi:10.1007/s10637-020-00993-4

Abstract

SummaryBackground Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7–80.1); doubling-time 6.2 months (range 1.4–36.6) and baseline testosterone 319.1 ng/ml (range 2.5–913.7). Median duration of therapy was 6.5 months (2.6–14.0). CTCs (median 48.5 cells/4 ml (range 15–268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by ≥50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or toxicity. Conclusions Use of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned.Trial registration number, date of registration - NCT02796898, June 13, 2016

Highlights

Androgen deprivation therapy (ADT) is a standard treatment for a biochemically recurring prostate cancer (BRPC) after definitive local therapy when salvage treatment directed at the prostate or prostate bed is not indicated [1]
We report the safety and potential clinical benefit of SM-88 used with MPS in patients with non-castrate non-metastatic BRPC who were being considered for ADT
Other endpoints were disease control defined by posttherapy changes in prostate-specific antigen (PSA), CTC, and imaging, were assessed by: rising PSA i.e. exclusive of the first 12 weeks of therapy, with >25% increase, and an absolute value >2 ng/ml); and local or metastatic progression by CT and bone scan mandated at study end (6 months after SM-88 start) or earlier if clinically indicated as determined by the local investigator

Summary

PHASE II STUDIES

Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer. Summary Background Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, nonmetastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. The median PSA was 6.4 ng/ml (range 1.7–80.1); doubling-time 6.2 months (range 1.4–36.6) and baseline testosterone 319.1 ng/ml (range 2.5– 913.7). CTCs (median 48.5 cells/4 ml (range 15–268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of

Introduction

Results

Average on Treatment

Lactose intolerance

Compliance with ethical standards