Originally published as JCO Early Release 10.1200/JCO.2008.17.4706 on November 3 2008

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Randomized, Phase II Study of the Thrombospondin-1-Mimetic Angiogenesis Inhibitor ABT-510 in Patients With Advanced Soft Tissue Sarcoma

Laurence H. Baker, Eric K. Rowinsky, David Mendelson, Rod A. Humerickhouse, Raymond A. Knight, Jiang Qian, Robert A. Carr, Gary B. Gordon, George D. Demetri

From the University of Michigan Medical School, Ann Arbor, MI; Cancer Therapy and Research Center, San Antonio, TX; Premiere Oncology of Arizona, Scottsdale, AZ; Abbott Laboratories, Abbott Park, IL; and Ludwig Center at Dana-Farber/Harvard Cancer Center, Boston, MA

Corresponding author: Laurence H. Baker, DO, University of Michigan Medical School, 24 Frank Lloyd Wright Dr, PO Box 483, Ann Arbor, MI 48106; e-mail: bakerl{at}umich.edu

Purpose Sarcomas are among the most proangiogenic malignancies in preclinical models. Phase I study results for ABT-510, which inhibits angiogenesis via a novel thrombospondin-mimetic mechanism, suggested activity in soft tissue sarcoma (STS) patients. This phase II study further evaluated the safety and efficacy of ABT-510 in advanced STS patients.

Patients and Methods Patients with metastatic or unresectable STS were randomly assigned to treatment with one of two ABT-510 dose schedules (20 mg once a day [20 mg], n = 42; or 100 mg twice a day [200 mg], n = 46), which were self-administered subcutaneously in 28-day treatment periods. End points included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and safety.

Results Median PFS for the 20-mg arm was 94 days, with 4- and 6-month PFS rate estimates of 42% and 24%, respectively. Median PFS for the 200-mg arm was 64 days, with 4- and 6-month PFS rate estimates of 41% and 32%, respectively. Although only one objective response was noted, stable disease was observed in 52% (20 mg) and 48% (200 mg) of patients. Median OS was 431 days (20 mg) and 295 days (200 mg). ABT-510 was well tolerated. Rare treatment-related grade 3 or 4 adverse events were one event each of hypotension, deep vein thrombosis, and hypophosphatemia. ABT-510 pharmacokinetics were dose proportional, time independent, and consistent with those in previous studies.

Conclusion ABT-510 had a favorable safety profile, and the rate of disease control and OS times were encouraging. However, with low ORR and lack of dose response, the study failed to yield compelling evidence of strong single-agent activity in STS.

published online ahead of print at www.jco.org on November 3, 2008.

Supported in part by funding from Abbott Laboratories; The Virginia and Daniel K. Ludwig Trust for Cancer Research, the Rubenstein Foundation, the Quick Family Fund for Cancer Research, the Ronald O. Perelman Fund for Cancer Research at Dana-Farber Cancer Institute, and Leslie's Links (G.D.D.); and the Walther Foundation and the Robert Ulrich Sarcoma Fund (L.H.B.)

Presented in part at the 41st Annual Meeting of the American Society of Oncology, May 13-17, 2005, Orlando, FL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00061659 [ClinicalTrials.gov] .

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