A phase II study of ABT-510 for the treatment of metastatic melanoma.
A phase II study of ABT-510 for the treatment of metastatic melanoma.
复制标题
ABT-510 治疗转移性黑色素瘤的 II 期研究。
DOI：
10.1200/jco.2006.24.18_suppl.8041
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
R. Humerickhouse
中科院分区：
文献类型：
--
作者：
S. Markovic;V. Suman;R. Rao;E. Creagan;W. Maples;J. Kaur;R. McWilliams;J. Allred;H. Pitot;G. Croghan;R. Humerickhouse
8041背景：ABT-510是一种凝血反应蛋白-1的合成肽类似物，可抑制VEGF/bFGF介导的人内皮细胞迁移、增殖、小管形成、角膜新生血管形成以及体内肿瘤生长（B16F10黑色素瘤）。在I期试验中被发现是安全的，ABT-510已进入II期试验。这是一项使用ABT-510治疗IV期黑色素瘤的II期研究的结果。
8041 Background: ABT-510 is a synthetic peptide analog of thrombospondin-1 demonstrating inhibition of VEGF/bFGF mediated human endothelial cell migration, proliferation, tube formation, cornea-neovascularization as well as inhibition of tumor growth in vivo (B16F10 melanoma). Having been found to be safe in phase I testing, ABT-510 has entered phase II trials. Presented are the results of a phase II study using ABT-510 for the treatment of stage IV melanoma.
METHODS
A two stage phase II clinical trial was conducted to assess the anti-tumor activity, safety profile and pharmacodynamics of ABT510 in patients with stage IV melanoma. Patients self-administered 100mg of ABT-510 subcutaneously twice/day. Therapy was continued in the absence of excessive toxicity or tumor progression. Primary endpoint was 18 week progression free survival rate. Enrolled were patients at least 18 years of age with measurable (RECIST) metastatic melanoma, ECOG performance status of 0-2 and normal pre-registration blood tests. Exclusion criteria included: cancer therapy less than 4 weeks prior to registration; failure to recover from prior therapy; brain metastases; significant recent bleeding; uncontrolled hypertension; and ongoing anti-coagulation. Pregnant or nursing women were not eligible.
RESULTS
Twenty-one patients (67% male) were enrolled with a median age of 55 years. Most patients had M1c disease (80%) and 62% had prior chemotherapy for stage IV melanoma. None of the patients were ineligible/canceled participation. After the first stage of the trial was complete, only 3 of the first 20 patients enrolled were progression-free at 18 weeks. Having not met the minimal clinical efficacy requirement (at least 7 of the first 20 patients progression-free at 18 weeks) the trial was closed to further accrual. Correlative laboratory studies suggested decreases in some of the measured parameters of angiogenesis (VEGFC, circulating endothelial cells) with no impact on immune homeostasis.
CONCLUSIONS
Single agent ABT-510 therapy administered at 100mg twice/day to patients with previously treated metastatic melanoma did not demonstrate significant clinical efficacy. However, changes in measured parameters of angiogenesis suggest possible clinical efficacy with higher dosing or in combination with cytotoxic therapy. [Table: see text].