Clinical Trials /

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

NCT03403634

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Celecoxib, Recombinant Interferon Alfa-2b, and Rintatolimod in Treating Patients With Colorectal Cancer Metastatic to the Liver
  • Official Title: Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver

Clinical Trial IDs

  • ORG STUDY ID: I 52917
  • SECONDARY ID: NCI-2017-02471
  • SECONDARY ID: I 52917
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03403634

Conditions

  • 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

Interventions

DrugSynonymsArms
CelecoxibBenzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177Treatment (celecoxib, interferon alfa-2b, rintatolimod)
Recombinant Interferon Alfa-2bAlfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Interferon Alfa-2B, Interferon Alpha-2b, Intron A, Sch 30500, Urifron, ViraferonTreatment (celecoxib, interferon alfa-2b, rintatolimod)
RintatolimodAmpligen, AtvogenTreatment (celecoxib, interferon alfa-2b, rintatolimod)

Purpose

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.

Detailed Description

      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

        -  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 QD on days 1, 2,3,8,9,10,15,16 and 17
      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (celecoxib, interferon alfa-2b, rintatolimod)ExperimentalPatients receive celecoxib orally PO BID, recombinant interferon alfa-2b IV QD over 20 minutes, and rintatolimod IV QD on days 1, 2, 3, 8, 9, 10, 15, 16 and 17 in the absence of disease progression or unacceptable toxicity.
  • Celecoxib
  • Recombinant Interferon Alfa-2b
  • Rintatolimod

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

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in tumor-infiltrating lymphocytes (TILs) in the colorectal cancer lesions
Time Frame:Baseline up to 12 months
Safety Issue:
Description:The TILs will be summarized by time-point (pre-/post-treatment) using the mean, median, standard deviation; and graphically using dot-plots. A 90% confidence interval for the mean change in TILs will be obtained using standard methods.

Secondary Outcome Measures

Measure:Incidence of adverse events according to Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 12 months
Safety Issue:
Description:Safety profile will be characterized by type, frequency, severity, timing, seriousness and relationship to study treatment.
Measure:Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1
Time Frame:Up to 12 months
Safety Issue:
Description:Will be treated as binary data and summarized using frequencies and relative frequencies; with the ORR estimated using a 90% confidence interval obtained using Jeffrey's prior method.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated

December 17, 2019