Phase II study of ruxolitinib in patients with pStat3+ breast cancer

Autor: Vivian W. Wang, Kornelia Polyak, Jane E. Brock, Nan Lin, Erica L. Mayer, Aditya Bardia, Ian E. Krop, Marie Iannone, Beth Overmoyer, Rebecca Gelman, Eric P. Winer
Rok vydání: 2013
Předmět:
Zdroj: Journal of Clinical Oncology. 31:TPS1134-TPS1134
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2013.31.15_suppl.tps1134
Popis: TPS1134 Background: Multiple lines of evidence implicate the IL-6/JAK2/Stat3 signaling pathway in metastatic progression and therapeutic resistance in breast cancer (Marotta et al, JCI2011; Britschgi et al, Cancer Cell 2012). Ruxolitinib, an oral inhibitor of JAK1 and JAK2, is approved for the treatment of intermediate or high-risk myelofibrosis, but has not been extensively tested in solid tumors. Methods: Pts with triple-negative breast cancer or inflammatory breast cancer of any subtype are eligible for prescreening of archival tumor tissue for pStat3 expression by immunohistochemistry. Pts with high (Cohort A; T-score >5) or low (Cohort B; T-score 3-4) pStat3 expression, measurable disease, adequate organ function, ECOG PS 0-2, and progression through > 1 line of prior therapy may proceed to receive ruxolitinib, 25 mg orally twice daily. Staging studies are performed at baseline (BL) and every 8 weeks (wk). Baseline tumor biopsy is required for pts who have accessible disease, with an optional biopsy at progression. Blood for IL-6, CRP, and circulating tumor cells are collected at BL, Wk 4, and off-treatment. Patient reported outcomes including EORTC QLQ C-30 and the M.D. Anderson Symptom Inventory are collected at BL, Wk 4, Wk 8, and off-treatment. Statistical Considerations: The primary endpoint of this open-label phase 2 trial is objective response by RECIST 1.1. The study is designed to distinguish between a response rate of 5% versus 20% in each cohort, separately. If > 2 responses out of 21 pts are observed in the first stage of Cohort A, a further 20 pts will be entered on that cohort; the agent will be deemed worthy of further study if > 5 of the total 41 pts achieve an objective response (power 0.90, type I error 0.046). Cohort B will open to accrual if Cohort A passes the first stage. If > 2 responses out of 21 pts are observed in the first stage of Cohort B, a further 20 patients will be entered into Cohort B, and the agent will be deemed worthy of further study if > 5 of the total 41 pts achieve an objective response (power 0.90, type I error 0.046). Study Status: A total of 85 patients have consented for prescreening of tumor tissue. As of January 3, 2013, 5 of a planned 41 patients with high pStat3 IHC scores have been treated with ruxolitinib, and accrual is ongoing. Clinical trial information: NCT01562873.
Databáze: OpenAIRE
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