Phase II Trial Of Gemcitabine Plus Nab-Paclitaxel +/- OGX-427 In Patients With Metastatic Pancreatic Cancer

Patients with pancreatic cancer usually present with inoperable disease and systemic therapy becomes the primary form of treatment. The combination of gemcitabine plus nab-paclitaxel represents an appropriate front-line standard of care for patients with metastatic pancreatic cancer. However, poor outcomes with this disease warrant exploration of novel drugs with unique mechanisms of action. Preclinical evidence suggests that OGX-427 has shown promising activity in pancreatic cancer. In this trial, we will compare the overall survival of patients with previously untreated metastatic pancreatic cancer using OGX-427 with either gemcitabine/nab-paclitaxel or a placebo with gemcitabine/nab-paclitaxel.

Inclusion criteria

• Histologically- or cytologically confirmed pancreatic adenocarcinoma
• Stage IV disease (measurable disease NOT required)
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
• At least 18 years of age
• Female patients who are not of child-bearing potential, and fertile female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of randomization.
• Fertile male patients willing to use adequate contraceptive measures.
• Adequate bone marrow, renal, and hepatic function.
• Ability to understand the nature of this study protocol, comply with study and/or follow-up procedures, and give written informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

• Any prior systemic or investigational therapy for metastatic pancreatic cancer. Systemic therapy administered alone or in combination with radiation in the adjuvant or neoadjuvant setting is permissible as long as it was completed > 6 months prior to the time of study randomization.
• History of other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study.
• Presence of known central nervous system or brain metastases.
• Known human immunodeficiency virus (HIV) infection.
• Active second invasive malignancy (except non-melanomatous skin cancer), defined as any malignancy with current need for cancer therapy or high possibility (>30%) of recurrence during the study.
• Patients receiving warfarin. However, therapeutic anticoagulation with Low Molecular Weight Heparin (LMWH) is allowed.
• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
• Current sensory neuropathy > Grade 1.
• Major surgery within 4 weeks of the start of study treatment (defined as those surgeries that require general anesthesia. Insertion of a vascular access device is NOT considered major surgery.). Patients must have recovered from the side effects of any major surgery prior to randomization.