Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial
| Autor: | Peter J. O'Dwyer, Chihche Lin, Lewis C. Strauss, T.R. Jeffry Evans, Joseph D. Purvis, Eric Van Cutsem, Alexander S. Rosemurgy, Malcolm J. Moore, Francis P. Arena, Elizabeth Armstrong, Michelle Gara, Edwin P. Rock, Jennifer Lee |
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| Rok vydání: | 2012 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty endocrine system diseases biology business.industry medicine.disease biology.organism_classification Placebo Gemcitabine Surgery Double blind Dasatinib hemic and lymphatic diseases Internal medicine Medicine Adenocarcinoma In patient Src family kinase Paca business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 30:TPS4134-TPS4134 |
| ISSN: | 1527-7755 0732-183X 0139-5017 |
| Popis: | TPS4134 Background: Dasatinib, a potent oral BCR-ABL and SRC family kinase (SFK) inhibitor, is approved for first- and second-line therapy of Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML) in pts with newly diagnosed CML or CML resistant/intolerant to prior therapy. SRC expression and activity is upregulated in PaCa and correlates with reduced survival in resected high-grade PaCa (Morton, Gastroenterology 2010) and resistance to Gem, a PaCa standard of care (Duxbury, J Am Coll Surg 2004). In preclinical PaCa studies, inhibition of SFKs with dasatinib reduces tumor cell proliferation, migration, and invasion; increases apoptosis; sensitizes cells to Gem; and inhibits development of metastases in vivo either alone or in combination with Gem (Duxbury, Clin Cancer Res 2004; Duxbury, J Am Coll Surg 2004; Nagaraj, Mol Cancer Ther 2010; Morton, op cit). Phase I clinical studies of dasatinib and Gem therapy in PaCa have demonstrated feasibility and suggested efficacy of the combination (Uronis, ASCO 2009, abstract e15506). Methods: This double-blind phase II study tests whether addition of dasatinib to Gem is tolerable and improves efficacy in pts with histologically/cytologically confirmed unresectable locally advanced nonmetastatic PaCa. Eligible pts, aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and adequate organ function, are randomized 1:1 to Gem 1000 mg/m2 IV once weekly (Weeks 1–3 of a 4-week cycle) plus either dasatinib 100 mg once daily or matched placebo. Pts are treated until progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoint is OS, and secondary endpoints are progression-free survival and safety. Exploratory endpoints include freedom from distant metastases, measures of pain and fatigue, overall response rate, and carbohydrate antigen 19-9. Final study analysis will be conducted after 135 deaths; all pts will be followed for survival. To date, 23/200 pts have enrolled; estimated primary completion date is March 2013. ClinicalTrials.gov identifier: NCT01395017. |
| Databáze: | OpenAIRE |
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