A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma

Purpose: Localized pancreatic carcinoma is rarely resectable and is resistant to conventional therapies. ONYX-015 (dl1520) is an E1B-55kD gene-deleted replication-selective adenovirus that preferentially replicates in and kills malignant cells. Endoscopic ultrasound (EUS) has the potential to conveniently and accurately deliver local therapy to the pancreas. Therefore, we undertook a trial of the feasibility, tolerability, and efficacy of EUS injection of ONYX-015 into unresectable pancreatic carcinomas. Experimental Design: Twenty-one patients with locally advanced adenocarcinoma of the pancreas or with metastatic disease, but minimal or absent liver metastases, underwent eight sessions of ONYX-015 delivered by EUS injection into the primary pancreatic tumor over 8 weeks. The final four treatments were given in combination with gemcitabine (i.v., 1000 mg/m(2)). Patients received 2 x 10(10) (n = 3) or 2 x 10(11) (n = 18) virus particles/treatment. Results: After combination therapy, 2 patients had partial regressions of the injected tumor, 2 had minor responses, 6 had stable disease, and 11 had progressive disease or had to go off study because of treatment toxicity. No clinical pancreatitis occurred despite mild, transient elevations in lipase in a minority of patients. Two patients had sepsis before the institution of prophylactic oral antibiotics. Two patients had duodenal perforations from the rigid endoscope tip. No perforations occurred after the protocol was changed to transgastic injections only. Conclusions: This study indicates that ONYX-015 injection via. EUS into pancreatic carcinomas by the transgastic route with prophylactic antibiotics is feasible and generally well tolerated either alone or in combination with gemcitabine. Transgastric EUS-guided injection is a new and practical method of delivering biological agents to pancreatic tumors.