A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas

Quincy S C Chu, Bahram Forouzesh, Samira Syed, Monica Mita, Garry Schwartz, Joshua Copper, Janet Curtright, Eric K. Rowinsky

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

This phase II study evaluated the antitumor activity of the tetracycline analog COL-3, a potent inhibitor of metalloproteinases (MMPs), particularly MMP-2 and MMP-9, on a continuous oral schedule at a dose of 50 mg/m2 daily in patients with advanced and/or metastatic soft tissue sarcoma (STS). The principal endpoints were the rate of objective tumor regression and the proportion of patients who did not experience disease progression during the first 8 weeks of treatment. Other study objectives included an assessment of pharmacology of COL-3, time to progression (TTP), and overall survival. A Simon two-stage design with multinomial stopping rule was employed, with 15 patients enrolled during the first stage of the study. Although COL-3 was generally well-tolerated, there were no objective responses and 5(33%) patients experienced disease progression during the first 8 weeks of treatment, which exceeded the criteria established a priori with regard to pursuing further evaluations of COL-3 in STS. The median values for TTP and survival were 109 and 279 days, respectively. Based on these results, further studies of COL-3 on this administration schedule in patients with STS are not warranted.

Original languageEnglish (US)
Pages (from-to)359-367
Number of pages9
JournalInvestigational New Drugs
Volume25
Issue number4
DOIs
StatePublished - Aug 2007

Keywords

  • COL-3
  • Metalloproteinase inhibitor
  • Soft tissue sarcoma

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas'. Together they form a unique fingerprint.

Cite this