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A phase I dose-escalation study of SR271425, an intravenously dosed thioxanthone analog, administered weekly in

A Craig Lockhart1, Emiliano Calvo, Anthony W Tolcher

  • 1Vanderbilt University Medical Center, Nashville, Tennessee, USA. Craig.Lockhart@Vanderbilt.edu

American Journal of Clinical Oncology
|February 6, 2009
PubMed
Abstract

Insights

The novel cytotoxic drug SR271425 showed a safe profile in advanced cancer patients, with no dose-limiting toxicities observed up to 675 mg/m/wk. Further development was halted, preventing the determination of a maximum tolerated dose.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • SR271425 is a novel thioxanthone analog with DNA-interacting cytotoxic properties.
  • Preclinical models demonstrated broad antitumor activity for SR271425.

Purpose of the Study:

  • To evaluate the safety and tolerability of SR271425 in patients with advanced cancer.
  • To determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD).
  • To assess the pharmacokinetic profile and preliminary efficacy of SR271425.

Main Methods:

  • A Phase I clinical trial was conducted, administering SR271425 intravenously weekly for 2 weeks, followed by 1 week rest.
  • Patients underwent cardiac assessments due to preclinical concerns of corrected QT (QTc) prolongation.
  • Dose escalation involved 18 patients across 5 dose levels (64–675 mg/m/wk).

Main Results:

  • No dose-limiting toxicities were identified throughout the study.
  • Grade 3 and 4 adverse events occurred in 55.6% and 22.2% of patients, respectively.
  • Grade 2 QTc prolongation was observed at higher doses, but no MTD was reached due to early program termination.

Conclusions:

  • SR271425 was safely administered up to 675 mg/m/wk on a 2-week on, 1-week off schedule.
  • The drug exhibited dose-proportional pharmacokinetics with a 6-hour half-life and no accumulation.
  • Despite promising preclinical data, the SR271425 program was terminated by the sponsor before MTD determination.

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