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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03403634
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE January 11, 2018
First Posted Date  ICMJE January 18, 2018
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE April 19, 2018
Estimated Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
Change in tumor-infiltrating lymphocytes (TILs) in the colorectal cancer lesions [ Time Frame: Baseline up to 12 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
  • Incidence of adverse events according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months ]
    Safety profile will be characterized by type, frequency, severity, timing, seriousness and relationship to study treatment.
  • Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1 [ Time Frame: Up to 12 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
  • Incidence of adverse events according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months ]
    Safety profile will be characterized by type, frequency, severity, timing, seriousness and relationship to study treatment.
  • Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1 [ Time Frame: Up to 12 months ]
    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.
  • Overall survival [ Time Frame: From the start of treatment until death due to any cause or last follow-up, assessed up to 12 months ]
    Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods.
  • Progression free survival [ Time Frame: From the start of treatment until disease progression (defined by RECIST 1.1) or last-follow-up, assessed up to 12 months ]
    Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods.
Current Other Pre-specified Outcome Measures
 (submitted: January 22, 2019)
  • Progression free survival [ Time Frame: From the start of treatment until disease progression (defined by RECIST 1.1) or last-follow-up, assessed up to 12 months ]
    Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods.
  • Overall survival [ Time Frame: From the start of treatment until death due to any cause or last follow-up, assessed up to 12 months ]
    Will be treated as bivariate time-to-event data and will be summarized using standard Kaplan-Meier methods.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Celecoxib, Recombinant Interferon Alfa-2b, and Rintatolimod in Treating Patients With Colorectal Cancer Metastatic to the Liver
Official Title  ICMJE Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Celecoxib
    Given PO
    Other Names:
    • Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-
    • Celebrex
    • SC-58635
    • YM 177
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Recombinant Interferon Alfa-2b
    Given IV
    Other Names:
    • Alfatronol
    • Glucoferon
    • Heberon Alfa
    • IFN alpha-2B
    • Interferon alfa 2b
    • Interferon Alfa-2B
    • Interferon Alpha-2b
    • Intron A
    • Sch 30500
    • Urifron
    • Viraferon
  • Drug: Rintatolimod
    Given IV
    Other Names:
    • Ampligen
    • Atvogen
Study Arms  ICMJE Experimental: Treatment (celecoxib, interferon alfa-2b, rintatolimod)
Patients 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.
Interventions:
  • Drug: Celecoxib
  • Other: Laboratory Biomarker Analysis
  • Biological: Recombinant Interferon Alfa-2b
  • Drug: Rintatolimod
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 17, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03403634
Other Study ID Numbers  ICMJE I 52917
NCI-2017-02471 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 52917 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Sarbajit Mukherjee, MD Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP