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

NCT03403634 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: I 52917NCI-2017-02471P01CA234212
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Change in Tumor-infiltrating Lymphocytes (TILs) in the Colorectal Cancer Lesions

  The TILs will be summarized by time-point (pre-/post-treatment) using the mean, median, standard deviation; and graphically using dot-plots. The TIL of interest is CD8a expression, which is reported as the mean fold change from pre-treatment (i.e. post treatment / pre treatment).

  Baseline up to 12 months

Secondary Outcomes (2)

• Number of Participants With Indicated Grade Adverse Event

  Up to 12 months

• Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1

  Up to 12 months

Other Outcomes (2)

• Progression Free Survival

  From the start of treatment until disease progression (defined by RECIST 1.1) or last-follow-up, assessed up to 12 months

• Overall Survival

  From the start of treatment until death due to any cause or last follow-up, assessed up to 12 months

Study Arms (1)

Treatment (celecoxib, interferon alfa-2b, rintatolimod)

EXPERIMENTAL

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.

Drug: Celecoxib; Other: Laboratory Biomarker Analysis; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod

Interventions

Celecoxib DRUG

Given PO

Also known as: Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177

Treatment (celecoxib, interferon alfa-2b, rintatolimod)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (celecoxib, interferon alfa-2b, rintatolimod)

Recombinant Interferon Alfa-2b BIOLOGICAL

Given IV

Also known as: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, Interferon alfa 2b, Interferon Alfa-2B, Interferon Alpha-2b, Intron A, Sch 30500, Urifron, Viraferon

Treatment (celecoxib, interferon alfa-2b, rintatolimod)

Rintatolimod DRUG

Given IV

Also known as: Ampligen, Atvogen

Treatment (celecoxib, interferon alfa-2b, rintatolimod)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Celecoxib; Introns; Interferon alpha-2; poly(I).poly(c12,U)

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Kris Attwood
• Organization: Roswell Park Comprehensive Cancer Center

Kristopher.Attwood@Roswellpark.org

716-845-1300

Study Officials

• Sarbajit Mukherjee, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: January 18, 2018
• Study Start: April 19, 2018
• Primary Completion: December 23, 2020
• Study Completion: August 29, 2021
• Last Updated: March 2, 2022
• Results First Posted: March 2, 2022

Record last verified: 2022-02

Locations

US (1)