A Study of REOLYSIN® in Combination With Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma
A Study of REOLYSIN® in Combination With Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma
The purpose of this Phase 2 study is to investigate whether intravenous administration of
 REOLYSIN therapeutic reovirus in combination with gemcitabine is effective and safe in the
 treatment of patients with advanced pancreatic cancer.
Pancreatic cancer remains one of the most lethal cancers, ranking as the fourth leading cause
 of cancer death for both men and women. The American Cancer Society estimates that 37,170 men
 and women (18,830 men and 18,340 women) will be diagnosed with pancreatic cancer and 33,370
 men and women will die of pancreatic cancer in 2008.

 Activating KRAS mutations are the most frequent genetic abnormalities in pancreatic cancer
 (occurring in 75% to 95% of patients).

 REOLYSIN has been demonstrated to kill a wide variety of cells with mutations along the RAS
 pathway, including pancreatic cancer cells.

 The Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN given
 intravenously in combination with gemcitabine every 3 weeks in patients with advanced
 pancreatic cancer.

 Response is a primary endpoint of this trial. Tumors will be evaluated by CT scan within 14
 days of starting treatment, then at 6 weeks, and then every 6 weeks thereafter.

 The safety of the gemcitabine and REOLYSIN combination will be assessed by the evaluation of
 the type, frequency and severity of adverse events, changes in clinical laboratory tests,
 immunogenicity and physical examination.

 Patients may continue to receive therapy under this protocol, provided he/she has not
 experienced either progressive disease or unacceptable drug-related toxicity that does not
 respond to either supportive care or dose reduction.
Inclusion Criteria:

 -  have advanced or metastatic pancreatic adenocarcinoma who have not previously received
 any chemotherapy or biotherapy. Patients who have received radiotherapy with or
 without radiotherapy enhancers (such as low dose 5-FU) will be eligible.

 -  have evidence of measurable disease. However, lesions in a previous radiation field
 are considered non-evaluable for response. Therefore, patients must have a measurable
 lesion that is not in a previously irradiated field to be eligible.

 -  have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy or
 surgical procedures, i.e., all such effects must have resolved to Common Terminology
 Criteria for Adverse Events (CTCAE, Version 3.0) Grade ≤1. Surgery (except biopsies)
 must have occurred at least 28 days prior to study enrolment.

 -  have received NO radiotherapy within 28 days prior to receiving study drug.

 -  have an ECOG Performance Score ≤ 2.

 -  have a life expectancy of at least 3 months.

 -  absolute neutrophil count (ANC) ≥ 1.5 x 10^9 [SI units 10^9/L]; Platelets ≥ 100 x10^9
 [SI units 10^9/L] (without platelet transfusion); Serum creatinine ≤ 1.5 x ULN;
 Bilirubin ≤ 1.5 x ULN; AST/ALT ≤ 2.5 x ULN (≤ 5 x ULN if patients have liver
 metastasis).

 -  negative pregnancy test for females of childbearing potential.

 Exclusion Criteria:

 -  no concurrent therapy with any other investigational anticancer agent while on study.

 -  have a history of or current evidence of brain metastasis(es).

 -  be on immunosuppressive therapy; have known HIV infection or active hepatitis B or C.

 -  be a pregnant or breast-feeding woman.

 -  have clinically significant cardiac disease.

 -  have dementia or altered mental status that would prohibit informed consent.

 -  have any other severe, acute, or chronic medical or psychiatric condition or
 laboratory abnormality that may increase the risk associated with study participation
 or study drug administration or may interfere with the interpretation of study results
 and, in the judgment of the Principal Investigator, would make the patient
 inappropriate for this study.