A 2-arm Randomized Phase II Study of Carboplatin, Paclitaxel Plus Reovirus Serotype-3 Dearing Strain (Reolysin®) vs. Carboplatin and Paclitaxel in the First Line Treatment of Patients With Recurrent or Metastatic Pancreatic Cancer

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the pancreas that is recurrent or
metastatic

- Cytological confirmation not allowed

- Paraffin-embedded tissue from tumor blocks required

- Patients must have measurable disease, defined as one lesion that can be accurately
measured in at least one dimension per Response Evaluation Criteria In Solid Tumors
(RECIST) 1.1 (longest diameter to be recorded) as >= 10 mm by spiral computed
tomography (CT) scan (CT scan slice thickness no greater than 5 mm)

- Malignant lymph nodes will be considered measurable if they are >= 15 mm in
short axis

- For patients previously irradiated, the measurable lesion must be outside the
radiated field

- Patients must not have received any prior chemotherapy in metastatic setting;
patients who have received prior chemotherapy in the adjuvant setting will not be
eligible for our study;

- Patients should not have received prior Reolysin;

- Prior palliative radiation therapy or major surgery must have occurred at least
28 days prior to study enrollment;

- Prior minor surgeries (such as laparoscopies) must have occurred at least 14
days prior to study enrollment;

- Prior minor procedures such as biopsies and mediport placement must have
occurred at least 48 hours prior to study enrollment

- Eastern Cooperative Oncology Group (ECOG) status =< 1 (Karnofsky >= 70%)

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L SI units

- Platelet count >= 100 x10^9/L SI units

- Hemoglobin >= 8.5 g/dL

- Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 mL/min

- Bilirubin =< ULN (=< 2 x upper limit of normal [ULN] if it is non-rising for a period
of 10 days prior to initiation of therapy)

- Aspartete aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN

- Troponin I < ULN

- All patients must have signed an informed consent indicating that they are aware of
the neoplastic nature of their disease and have been informed of the procedures of
the protocol, the experimental nature of the therapy, alternatives, potential
benefits, side effects, risks, and discomforts

- The effects of Reolysin on the developing human fetus at the recommended therapeutic
dose are unknown; for this reason and because the other chemotherapeutic agents used
in this trial are known to be teratogenic, women of child-bearing potential and men
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study
participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately;
patients must be able to avoid direct contact with pregnant or nursing women, infants
and immunocompromised individuals while on study and for >= 3 weeks following the
last dose of Reolysin administration

- All patients must be willing and able to comply with scheduled visits, the treatment
plan, and laboratory tests

Exclusion Criteria:

- Patients may not be receiving any other investigational agents or concurrent therapy
with other anti-cancer agents while on study

- Patients with untreated brain metastases will be excluded from this clinical trial;
however, patients with resected oligometastasis are eligible if postresection
magnetic resonance imaging (MRI) demonstrates resolution; gamma-knife treated
patients are also eligible if there are no more than two treated metastases confined
to the same area of the brain and a post treatment MRI shows a decrease in the
metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Reolysin or other agents used in the study

- Patients may not have received any viral-based therapy within the past 6 months

- Patients must have NO continuing acute toxic effects (except alopecia) of any prior
radiotherapy, chemotherapy, or surgical procedures; all such effects must have
resolved to Common Terminology Criteria for Adverse Events (CTCAE, v. 4 ) Grade =< 1
prior to study enrollment

- Patients must not have grade 2 or higher baseline peripheral neuropathy according to
CTCAE v. 4

- Patients with uncontrolled cardiac dysfunction or arrhythmia, including a myocardial
infarction in the preceding 6 months, known cardiac ejection fraction < 40%,
symptomatic congestive heart failure, or unstable angina pectoris

- Patients must not be receiving concurrent systemic immunosuppressive therapy

- Patients must not have known human immunodeficiency virus (HIV) infection or active
hepatitis B or C

- Patients must not have uncontrolled intercurrent illness including, but not limited
to, ongoing or active infection or known psychiatric illness/social situations that
would limit compliance with study requirements

- Patients must not have dementia or altered mental status that would prohibit
informed consent

- Patients must not have other known severe, acute, or chronic medical or psychiatric
condition or laboratory abnormality that may increase the risk associated with study
participation, study drug administration, or may interfere with the interpretation of
study results that, in the judgment of the Principal Investigator, would make the
patient inappropriate for this study

- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects; because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with Reolysin,
breastfeeding should be discontinued while the mother is being treated with the
agents in this clinical trial