A randomized phase II study of SM-88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond

Cancer Med. 2022 Nov;11(22):4169-4181. doi: 10.1002/cam4.4768. Epub 2022 May 2.

Abstract

Background: This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1).

Results: Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor of 920 mg. SM-88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention-to-treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7-4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01).

Conclusions: SM-88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second-line treatment of patients with mPDAC.

Clinicaltrials: gov Identifier: NCT03512756.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / pathology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Humans
  • Methoxsalen / therapeutic use
  • Pancreatic Neoplasms* / pathology
  • Phenytoin / therapeutic use
  • Quality of Life
  • Sirolimus / adverse effects

Substances

  • Methoxsalen
  • Phenytoin
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT03512756