TY - JOUR
T1 - A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas
AU - Chu, Quincy S C
AU - Forouzesh, Bahram
AU - Syed, Samira
AU - Mita, Monica
AU - Schwartz, Garry
AU - Copper, Joshua
AU - Curtright, Janet
AU - Rowinsky, Eric K.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - COL-3
KW - Metalloproteinase inhibitor
KW - Soft tissue sarcoma
UR - http://www.scopus.com/inward/record.url?scp=34250630512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250630512&partnerID=8YFLogxK
U2 - 10.1007/s10637-006-9031-6
DO - 10.1007/s10637-006-9031-6
M3 - Article
C2 - 17237909
AN - SCOPUS:34250630512
VL - 25
SP - 359
EP - 367
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 4
ER -