Investigational New Drugs

, 25:359 | Cite as

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

  • Quincy S. C. ChuEmail author
  • Bahram Forouzesh
  • Samira Syed
  • Monica Mita
  • Garry Schwartz
  • Joshua Copper
  • Janet Curtright
  • Eric K. Rowinsky
Phase II Studies


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.


Metalloproteinase inhibitor COL-3 Soft tissue sarcoma 





Time to progression


Metalloproteinase inhibitor


Soft tissue sarcomas


Eastern Cooperative Group


Computerized tomography


Response evaluation criteria in solid tumours


High-performance liquid chromatography


Stable disease


Partial response


Complete response


Human Immunodeficiency Virus



The study was supported by a unrestricted grant from CollaGenex (Newton, PA).


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Quincy S. C. Chu
    • 1
    Email author
  • Bahram Forouzesh
    • 2
  • Samira Syed
    • 2
  • Monica Mita
    • 2
  • Garry Schwartz
    • 3
  • Joshua Copper
    • 2
  • Janet Curtright
    • 2
  • Eric K. Rowinsky
    • 2
  1. 1.Cross Cancer InstituteEdmontonCanada
  2. 2.Institute for Drug Development, Cancer Therapy and Research CenterUniversity of Texas Health Science CenterSan AntonioUSA
  3. 3.Brooke Army Medical CenterFort Sam HoustonUSA

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