Celecoxib, Recombinant Interferon Alfa-2b, and Rintatolimod in Treating Patients With Colorectal Cancer Metastatic to the Liver

PRIMARY OBJECTIVES:

I. To determine the impact of a chemokine-modulatory regimen on the immune microenvironment
of colorectal liver metastases, specifically the changes in the ratio between cytotoxic
T-lymphocyte (CTL) marker (CD8a gene expression) to regulatory T cell (Treg) markers (FoxP3
gene expression).

SECONDARY OBJECTIVES:

I. Estimate the objective response rate of a chemokine-modulatory regimen in metastatic
colorectal cancer (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).

II. Examine the safety and tolerability profile of the combination of recombinant interferon
alfa-2b (interferon alpha-2b), rintatolimod, and celecoxib when given as chemokine modulation
to colorectal cancer patients prior to surgical resection using the Cancer Therapy Evaluation
Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE version 4.0).

TERTIARY OBJECTIVES:

- Estimate the median progression free survival of a chemokine-modulatory regimen in
metastatic colorectal cancer

- Estimate overall survival in participants with recurrent and/or metastatic unresectable
colorectal cancer who received the chemokine-modulatory regimen

- To conduct correlative science studies including:

- Comparison (using RT-PCR, immunofluorescence [IF] and immunohistochemistry [IHC] on
serial sections) of the metastatic tissue specimen with regard to total numbers of
infiltrating T cells, their CD4/CD8 ratios, frequencies of FoxP3 cells, and the
expression of chemokine receptors on CD4+ and CD8+ T cells (CXCR3, CCR5, CCR4, CCR6, and
CXCR4)

- Evaluate the local expression of effector T cells (Teff)-attracting chemokines (CCR5,
CXCL9, CXCL10 and CXCL11) and Treg-favoring chemokines (CCL22 and CXCL12) using IF and
RT-PCR.

OUTLINE:

Patients receive celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b
intravenously (IV) over 20 minutes, and rintatolimod IV on days 1-3. Treatment repeats every
21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 12
months.

Inclusion Criteria:

- Recurrent and/or metastatic unresectable colorectal cancer with hepatic metastases

- Hepatic metastases present which are amenable to biopsy

- Prior treatment with, contra-indication to or refusal of a fluoropyrimidine,
irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wild-type [wt]) as
well as a PD-1 or PD-L1 targeted drug if MSI-H/dMMR

- No chemotherapy, radiotherapy, major surgery, or biologic therapy within 3 weeks of
protocol treatment

- An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Have measurable disease per RECIST 1.1 criteria present

- Ability to swallow and retain oral medication

- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
entry; should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately

- Platelet >= 75,000/uL

- Hemoglobin >= 9 g/dL

- Hematocrit >= 27%

- Absolute neutrophil count (ANC) >= 1500/uL

- Creatinine < = institutional upper limit of normal (ULN) OR

- Creatinine clearance >= 50 mL/min for patients with creatinine levels greater than ULN

- Total bilirubin =< 1.5 X institutional ULN or for patients with known Gilbert's
Syndrome total bilirubin <= 3 x ULN

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
institutional ULN

- Serum amylase =< 1.5 X institutional ULN

- Lipase =< 1.5 X institutional ULN

- Participant or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

- Patients currently treated with systemic immunosuppressive agents, including steroids,
are ineligible until 3 weeks after removal from immunosuppressive treatment

- Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy
or history of transplantation

- Patients who are pregnant or nursing; women of childbearing potential (WOCBP) will
have to undergo a urine pregnancy test as part of screening

- Untreated central nervous system (CNS) metastases

- Cardiac risk factors including:

- Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial
infarction, or ischemia) within 3 months of signing consent

- Patients with a New York Heart Association classification of III or IV

- History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or
upper gastrointestinal perforation within the past 3 years; patients with ulceration,
bleeding or perforation in the lower bowel are not excluded

- Prior allergic reaction or hypersensitivity to sulfonamides, celecoxib, or
non-steroidal antiinflammatory drugs (NSAIDs)

- Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2
times per week (on average) or aspirin at more than 325 mg at least three times per
week, on average; low-dose aspirin not exceeding 100 mg/day is permitted; patients who
agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out
period is required

- Received an investigational agent within 30 days prior to enrollment

- Unwilling or unable to follow protocol requirements

- Patients with known serious mood disorders

- Any additional condition which in the investigator?s opinion deems the participant an
unsuitable candidate to receive the study drugs