Metastatic Carcinoma in the LiverPhase 2NCT03403634

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

A Phase 2 study testing Celecoxib, Laboratory Biomarker Analysis and Recombinant Interferon Alfa-2b in people with Metastatic Carcinoma in the Liver and Recurrent Colorectal Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Carcinoma in the Liver, Recurrent Colorectal Carcinoma, Stage IV Colorectal Cancer AJCC v7
What is being tested?: Celecoxib, Laboratory Biomarker Analysis and Recombinant Interferon Alfa-2b
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteUnited States
Study dates: 19 Apr 2018to 29 Aug 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 19Show fewer

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

Who cannot join

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

Show all 14Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Roswell Park Cancer Institute
Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver

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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

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
Being tested: Celecoxib, Laboratory Biomarker Analysis, Recombinant Interferon Alfa-2b, Rintatolimod
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CelecoxibDrug
Also called Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Recombinant Interferon Alfa-2bBiological
Also called Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B
Given IV
RintatolimodDrug
Also called Ampligen, Atvogen
Given IV

Study groups in NCT03403634
Study group	Role	What they receive
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. Receives: Drug: Celecoxib; Other: Laboratory Biomarker Analysis; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Baseline up to 12 months

Secondary outcomes (2)

Number of Participants With Indicated Grade Adverse Event
Safety profile will be characterized by type, frequency, severity, timing, seriousness and relationship to study treatment. The highest grade treatment related AE is provided (per Common Terminology Criteria for Adverse Events version 4.0).
Measured: Up to 12 months
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
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.
Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Apr 201829 Aug 2021

First posted18 Jan 2018
Study start19 Apr 2018
Primary completion23 Dec 2020
Study completion29 Aug 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Metastatic Carcinoma in the LiverStudies of the same condition, open and under way.
More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03403634
Sponsor's protocol ID: I 52917
Other IDs: NCI-2017-02471, I 52917, P01CA234212
Status last verified: Feb 2022
First submitted: 11 Jan 2018
Last updated: 2 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Hepatocellular Carcinoma, Renal Cell Carcinoma
Active, not recruitingPhase 2
Combined Treatment of Durvalumab, Bevacizumab, Tremelimumab and Transarterial Chemoembolization (TACE) in Subjects With Hepatocellular Carcinoma or Biliary Tract Carcinoma
Hepatocellular Cancer, Hepatocellular Carcinoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial
Advanced Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma

All Metastatic Carcinoma in the Liver trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 2a Study Evaluating a Chemokine-Modulatory Regimen in Patients With Colorectal Cancer Metastatic to the Liver
ClinicalTrials.gov ID: NCT03403634
Acronym / sponsor ID: I 52917
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
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Roswell Park Cancer InstituteUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 19 Apr 2018 (actual)
Primary completion: 23 Dec 2020 (actual)
Study completion: 29 Aug 2021 (actual)
First posted: 18 Jan 2018 (actual)
Results: Posted 2 Mar 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

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

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:

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (celecoxib, interferon alfa-2b, rintatolimod)	Experimental	Drug: Celecoxib, Other: Laboratory Biomarker Analysis, Biological: Recombinant Interferon Alfa-2b, Drug: RintatolimodPatients 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

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

Key exclusion criteria (14 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CelecoxibAlso: Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177Given PO	Drug	Treatment (celecoxib, interferon alfa-2b, rintatolimod)
Laboratory Biomarker AnalysisCorrelative studies	Other	Treatment (celecoxib, interferon alfa-2b, rintatolimod)
Recombinant Interferon Alfa-2bAlso: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2BGiven IV	Biological	Treatment (celecoxib, interferon alfa-2b, rintatolimod)
RintatolimodAlso: Ampligen, AtvogenGiven IV	Drug	Treatment (celecoxib, interferon alfa-2b, rintatolimod)

Primary outcome

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. The TIL of interest is CD8a expression, which is reported as the mean fold change from pre-treatment (i.e. post treatment / pre treatment).

2 secondary outcomes

Number of Participants With Indicated Grade Adverse Event
Time frame: Up to 12 months
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time frame: Up to 12 months

Results and safety

Results posted to the registry on 2 Mar 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod)	19	12

Primary outcome: Change in Tumor-infiltrating Lymphocytes (TILs) in the Colorectal Cancer Lesions

Time frame: Baseline up to 12 months. Mean (Standard Deviation). Unit: fold change

Measure	Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod) n = 12
Value	7.25 (13.79)

Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod): p = 0.046, t-test, 1 sided

Population analysed: 3 patients did not have post treatment biopsies, and were considered unevaluable for the primary endpoint.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was collected up to 30 days after end of treatment, up to 1 year.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment (Celecoxib, Interferon Alfa-2b, Rintatolimod)	3 of 15 (20%)	14 of 15 (93.3%)	8 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sarbajit Mukherjee, MD principal investigator

Roswell Park Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Tumor-infiltrating Lymphocytes (TILs) in the Colorectal Cancer Lesions (time frame: Baseline up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03403634.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.