Carboplatin and Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Metastatic Pancreatic Cancer

PRIMARY OBJECTIVES:

I. To assess the improvement in progression-free survival with Reolysin (wild-type reovirus),
carboplatin, and paclitaxel relative to carboplatin and paclitaxel alone in patients with
recurrent or metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of Reolysin in combination with carboplatin and
paclitaxel versus without Reolysin in patients with recurrent or metastatic pancreas cancer.

II. To compare the treatment groups for other efficacy endpoints such as overall response
rate and overall survival.

III. To define how the combination of Reolysin and carboplatin and paclitaxel (CP) modulate
factors regulating immunity to reovirus and its persistence in the system circulation of
patients with pancreatic cancer.

IV. To prospectively establish and validate the relationship between Ras mutations in tumor
samples and response to Reolysin.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30
minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every
21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive paclitaxel and carboplatin as in Arm I. Courses repeat every 21 days
in the absence of disease progression or unacceptable toxicity. Patients with disease
progression may crossover to Arm I.

After completion of study treatment, patients are followed up at 1 month and then every 2
months thereafter.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the pancreas that is recurrent or
metastatic; cytological confirmation is not allowed on this study; paraffin embedded
tissue from tumor blocks will be required from patients before enrolling on this
study; diagnosis of pancreas cancer with histologic confirmation of adenocarcinoma
would suffice

- 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 International System of Units (SI)
units

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

- Hemoglobin >= 8.5 g/dL SI units

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

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

- Aspartate 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

- 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, version [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; breastfeeding should be discontinued
while the mother is being treated with the agents in this clinical trial