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

Benjamin A Gartrell, Mack Roach 3rd, Avi Retter, Gerald H Sokol, Giuseppe Del Priore, Howard I Scher, Benjamin A Gartrell, Mack Roach 3rd, Avi Retter, Gerald H Sokol, Giuseppe Del Priore, Howard I Scher

Abstract

Background 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.

Keywords: Metabolism based therapy; Prostate Cancer; SM-88.

Conflict of interest statement

NY Cancer and Blood received research support from TYME. GHS and GDP are employees or board members at TYME and received salary, equity and other support.

Figures

Fig. 1
Fig. 1
Swimmer’s Plot of Radiographic or PSA Progression Free Survival
Fig. 2
Fig. 2
Individual CTC Results By Radiographic Progression
Fig. 3
Fig. 3
PSA Values Before Treatment
Fig. 4
Fig. 4
Waterfall Plot of Individual Patient PSA Values – By CTC Group. Blue bars indicate patients with local (one with prostate bed) or regional progression (2 with pelvic node)
Fig. 5
Fig. 5
CTC Nadir on SM-88 And PSA or Radiographic Progression
Fig. 6
Fig. 6
Quality of Life And Sexual Health EORTC Questionnaire

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Source: PubMed

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