Celecoxib, Recombinant Interferon Alfa-2b, and Rintatolimod in Treating Patients With Colorectal Cancer Metastatic to the Liver
Condition: Metastatic Carcinoma in the Liver; Recurrent Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7
MeSH terms: Carcinoma; Colorectal Neoplasms
Intervention: Celecoxib; Laboratory Biomarker Analysis; Recombinant Interferon Alfa-2b; Rintatolimod
Intervention description: Given PO; Correlative studies; Given IV; Given IV
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; poly(I).poly(c12,U); Celecoxib; Benzenesulfonamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This early phase IIA trial studies how well celecoxib, recombinant interferon alfa-2b, and
      rintatolimod work in treating patients with colorectal cancer that as spread to the liver.
      Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Recombinant interferon alfa-2b is a substance that can improve the body's natural
      response and may interfere with the growth of tumor cells. Rintatolimod may stimulate the
      immune system. Giving celecoxib, recombinant interferon alfa-2b, and rintatolimod may work
      better at treating colorectal cancer that has spread to the liver.
    

Eligibility criteria:

        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

          -  Plasma 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 celecoxib, or non-steroidal
             antiinflammatory drugs (NSAIDs) or any study agents which would prevent completion of
             protocol therapy

          -  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