Colorectal CancerPhase 1/2NCT01545141
Chemokine-Modulatory Regimen for Recurrent Resectable Colorectal Cancer
A Phase 1/2 study testing Chemokin Modulatory Regimen (5 MU/m2), Chemokin Modulatory Regimen (10 MU/m2) and Chemokin Modulatory Regimen (20 MU/m2) in people with Colorectal Cancer and Colorectal Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
Determine the safety of a combination of IFN, celecoxib, and rintatolimod for patients with recurrent colorectal cancer. This will also test whether the above combination can help the immune system to fight the tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors
- What is being tested?
- Chemokin Modulatory Regimen (5 MU/m2), Chemokin Modulatory Regimen (10 MU/m2) and Chemokin Modulatory Regimen (20 MU/m2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to 8 Apr 2017
- Phase
- Phase 1/2
- 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 resectable colorectal cancer, including disease within the abdomen and pelvis with no evidence of extra-abdominal metastases. Isolated resectable pulmonary metastasis are allowable in the absence of intra-abdominal metastasis. Intra-abdominal disease includes: isolated hepatic metastasis/metastases (see next inclusion criteria point), isolated peritoneal metastasis, peritoneal carcinomatosis (including patients undergoing cytoreductive surgery alone or in combination with hyperthermic intraperitoneal chemoperfusion - HIPEC), or a combination of hepatic and extrahepatic metastasis.
- Patients with isolated hepatic metastasis must satisfy a Clinical Risk Score of 3 or higher (see Appendix C)
- Eligible patients are expected to have a complete resection based on preoperative imaging. Any patient not found to be able to have complete resection will not be eligible for this study.
- No chemotherapy, radiotherapy, major surgery, or biologic therapy within 3 weeks of protocol treatment
- An ECOG performance status of 0, 1, or 2.
- Age equal to 18 years or older.
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- Must have normal organ and marrow function as defined below:
- Platelet ≥ 75,000/µL
- Hemoglobin ≥ 9.0 g/dL
- Hematocrit ≥ 27.0%
- Absolute Neutrophil Count (ANC) ≥ 1500/µL
- Creatinine < institutional upper limit of normal (ULN) OR
- Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels greater than ULN
- Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN)
- AST(SGOT) and ALT(SGPT) ≤ 2.5 X institutional upper limit of normal (ULN)
- Serum amylase and lipase within normal limits.
- Patient must be able to understand and be willing to sign a written informed consent document.
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 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.
- Patients with comorbid medical conditions that render them unfit for surgery.
- Metastatic or recurrent disease that is deemed partially resectable or unresectable based on preoperative imaging.
- Metastatic disease outside the confines of the abdomen, pelvis and thorax (e.g bone, brain)
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- 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 (Appendix A)
- 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 sulfonamides, celecoxib, or NSAIDs.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Randomized Phase 1/2 Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer
Determine the safety of a combination of IFN, celecoxib, and rintatolimod for patients with recurrent colorectal cancer. This will also test whether the above combination can help the immune system to fight the tumors. The results will allow the investigators to determine the "preferred" combination for subsequent extended studies.
Read the detailed description
A previously-demonstrated correlation between the density of CRC-infiltrating effector T cells and long-term outcomes (Galon et al., 2006; Pages et al., 2005) has been established. In preclinical ex vivo studies performed using explants of resected metastatic CRC, the combination of IFNα with nonselective or COX2-selective inhibitors of prostaglandin synthesis resulted in elevated production of the effector T cell-attracting chemokines CXCL10 and CCL5. This was associated with concomitant suppression of the intratumoral expression of CCL22, a Treg-attracting chemokine (Muthuswamy et al 2008 Canc Res, and Muthuswamy et al, submitted to Canc Res 2011). However, in a subset of patients, the optimal results, particularly with regard to CCL5 induction, required additional stimulation by a third agent, poly-I:C (a toll-like receptor -TLR Ligand).
Therefore, the investigators seek to establish the safety profile of a novel chemokine regimen consisting of IFN, celecoxib and poly-I:C. The investigators also hypothesize that the proposed neoadjuvant chemokine modulation treatment in recurrent CRC patients undergoing tumor resection may increase the density of tumor infiltrating lymphocytes (TILS).
In addition, treatment in the neoadjuvant setting will allow a comparative analysis of the effect of chemokine modulation on the local recruitment of effector-type T cells and the de-recruitment of Treg within resected tumor tissues; helping to determine the "preferred" chemokine-modulating regimen for subsequent extended studies. Such prospective studies will focus on using combinations of chemokine modulation and cancer vaccines in patients with CRC. The investigators have, for example, recently observed that αDC1, a new type of DC vaccine (Kalinski and Okada, 2010; Mailliard et al., 2004) is particularly effective in inducing the effector pathway of T cells differentiation. This was manifested by the induction of tumor-killing function and the induction of effector-type chemokine receptors (CXCR3 and CCR5) (Kalinski and Okada, 2010; Watchmaker et al., 2010). Combining the αDC1 vaccine to a safe, tolerable and efficacious CKM regimen may hold promise for patients with poor prognostic CRC.
- Being tested
- Chemokin Modulatory Regimen (5 MU/m2), Chemokin Modulatory Regimen (10 MU/m2), Chemokin Modulatory Regimen (20 MU/m2)
- Keywords
- metastatic, recurrent, peritoneal metastasis, cytoreductive surgery, hyperthermic intraperitoneal chemoperfusion, HIPEC, hepatic metastasis, extrahepatic metastasis, vaccine
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemokin Modulatory Regimen (5 MU/m2)Drug
Also called Celebrex, INTRON A, Interferon-alpha 2b, IFN-alpha
Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2.
Chemokin Modulatory Regimen (10 MU/m2)Drug
Also called Celebrex, INTRON A, Interferon-alpha 2b, IFN-alpha
Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery
Chemokin Modulatory Regimen (20 MU/m2)Drug
Also called Celebrex, INTRON A, Interferon-alpha 2b, IFN-alpha
Celecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery
| Study group | Role | What they receive |
|---|---|---|
| Surgery only | No intervention | Surgical resection only, performed as standard of care for the disease |
| Chemokin Modulatory Regimen (5 MU/m2) | Experimental | Chemokine Modulatory Regimen monday through Friday prior to surgery:
400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Receives: Drug: Chemokin Modulatory Regimen (5 MU/m2) |
| Chemokin Modulatory Regimen (10 MU/m2) | Experimental | Chemokine Modulatory Regimen monday through Friday prior to surgery:
400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 10 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Receives: Drug: Chemokin Modulatory Regimen (10 MU/m2) |
| Chemokin Modulatory Regimen (20 MU/m2) | Experimental | Chemokine Modulatory Regimen monday through Friday prior to surgery:
400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days Receives: Drug: Chemokin Modulatory Regimen (20 MU/m2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Number of Tumor-infiltrating CD8+ Cells.
This will be assessed by the increase in the total number of tumor-infiltrating CD8+ T cells in the resected, recurrent CRC lesions (measured as the ratio between the CD8 mRNA message and the expression of the housekeeping gene HPRT), comparing Arm A and Arm B.
Measured: Day of surgery: day 8-10
Secondary outcomes (1)
Treatment Related Adverse Events
The number of adverse events experienced within 1 week of treatment. This was completed for the Phase II portion of the study.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2012 (estimated)
- Study startOct 2012
- Primary completion8 Apr 2016
- Study completion8 Apr 2017
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 Colorectal CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AIM ImmunoTech Inc.
- Responsible party
- Sponsor
- Investigators
- Amer H Zureikat, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545141
- Sponsor's protocol ID
- 10-131
- Other IDs
- 10-131
- Status last verified
- Oct 2023
- First submitted
- 29 Feb 2012
- Last updated
- 27 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 1/2 Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01545141
- Acronym / sponsor ID
- 10-131
- Keywords
- metastatic, recurrent, peritoneal metastasis, cytoreductive surgery, hyperthermic intraperitoneal chemoperfusion, HIPEC, hepatic metastasis, extrahepatic metastasis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- AIM ImmunoTech Inc.
- Study start
- Oct 2012
- Primary completion
- 8 Apr 2016 (actual)
- Study completion
- 8 Apr 2017 (actual)
- First posted
- 6 Mar 2012 (estimated)
- Results
- Posted 9 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determine the safety of a combination of IFN, celecoxib, and rintatolimod for patients with recurrent colorectal cancer. This will also test whether the above combination can help the immune system to fight the tumors. The results will allow the investigators to determine the "preferred" combination for subsequent extended studies.
Detailed description
A previously-demonstrated correlation between the density of CRC-infiltrating effector T cells and long-term outcomes (Galon et al., 2006; Pages et al., 2005) has been established. In preclinical ex vivo studies performed using explants of resected metastatic CRC, the combination of IFNα with nonselective or COX2-selective inhibitors of prostaglandin synthesis resulted in elevated production of the effector T cell-attracting chemokines CXCL10 and CCL5. This was associated with concomitant suppression of the intratumoral expression of CCL22, a Treg-attracting chemokine (Muthuswamy et al 2008 Canc Res, and Muthuswamy et al, submitted to Canc Res 2011). However, in a subset of patients, the optimal results, particularly with regard to CCL5 induction, required additional stimulation by a third agent, poly-I:C (a toll-like receptor -TLR Ligand).
Therefore, the investigators seek to establish the safety profile of a novel chemokine regimen consisting of IFN, celecoxib and poly-I:C. The investigators also hypothesize that the proposed neoadjuvant chemokine modulation treatment in recurrent CRC patients undergoing tumor resection may increase the density of tumor infiltrating lymphocytes (TILS).
In addition, treatment in the neoadjuvant setting will allow a comparative analysis of the effect of chemokine modulation on the local recruitment of effector-type T cells and the de-recruitment of Treg within resected tumor tissues; helping to determine the "preferred" chemokine-modulating regimen for subsequent extended studies. Such prospective studies will focus on using combinations of chemokine modulation and cancer vaccines in patients with CRC. The investigators have, for example, recently observed that αDC1, a new type of DC vaccine (Kalinski and Okada, 2010; Mailliard et al., 2004) is particularly effective in inducing the effector pathway of T cells differentiation. This was manifested by the induction of tumor-killing function and the induction of effector-type chemokine receptors (CXCR3 and CCR5) (Kalinski and Okada, 2010; Watchmaker et al., 2010). Combining the αDC1 vaccine to a safe, tolerable and efficacious CKM regimen may hold promise for patients with poor prognostic CRC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Surgery only | No intervention | –Surgical resection only, performed as standard of care for the disease |
| Chemokin Modulatory Regimen (5 MU/m2) | Experimental | Drug: Chemokin Modulatory Regimen (5 MU/m2)Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 5 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days |
| Chemokin Modulatory Regimen (10 MU/m2) | Experimental | Drug: Chemokin Modulatory Regimen (10 MU/m2)Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 10 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days |
| Chemokin Modulatory Regimen (20 MU/m2) | Experimental | Drug: Chemokin Modulatory Regimen (20 MU/m2)Chemokine Modulatory Regimen monday through Friday prior to surgery: 400 mg celecoxib for 5 days IFN by intravenous infusion (IV) (Phase 1 dose escalation of 20 MU/m2) for 5 days Rintatolimod 200 mg by IV infusion for 5 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Recurrent and/or metastatic resectable colorectal cancer, including disease within the abdomen and pelvis with no evidence of extra-abdominal metastases. Isolated resectable pulmonary metastasis are allowable in the absence of intra-abdominal metastasis. Intra-abdominal disease includes: isolated hepatic metastasis/metastases (see next inclusion criteria point), isolated peritoneal metastasis, peritoneal carcinomatosis (including patients undergoing cytoreductive surgery alone or in combination with hyperthermic intraperitoneal chemoperfusion - HIPEC), or a combination of hepatic and extrahepatic metastasis.
- Patients with isolated hepatic metastasis must satisfy a Clinical Risk Score of 3 or higher (see Appendix C)
- Eligible patients are expected to have a complete resection based on preoperative imaging. Any patient not found to be able to have complete resection will not be eligible for this study.
- No chemotherapy, radiotherapy, major surgery, or biologic therapy within 3 weeks of protocol treatment
- An ECOG performance status of 0, 1, or 2.
Key exclusion criteria (12 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 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.
- Patients with comorbid medical conditions that render them unfit for surgery.
- Metastatic or recurrent disease that is deemed partially resectable or unresectable based on preoperative imaging.
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 |
|---|---|---|
| Chemokin Modulatory Regimen (5 MU/m2)Also: Celebrex, INTRON A, Interferon-alpha 2b, IFN-alphaCelecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery IFN: i.v. administration, M-F of the week prior to scheduled surgery. Dose escalation evaluating 5, 10, and 20 MU/m2. | Drug | Chemokin Modulatory Regimen (5 MU/m2) |
| Chemokin Modulatory Regimen (10 MU/m2)Also: Celebrex, INTRON A, Interferon-alpha 2b, IFN-alphaCelecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery | Drug | Chemokin Modulatory Regimen (10 MU/m2) |
| Chemokin Modulatory Regimen (20 MU/m2)Also: Celebrex, INTRON A, Interferon-alpha 2b, IFN-alphaCelecoxib: 200 mg twice/day M-F of the week prior to scheduled surgery rintatolimod: 200 mg i.v. administration M-F of the week prior to scheduled surgery | Drug | Chemokin Modulatory Regimen (20 MU/m2) |
Primary outcome
Change in the Number of Tumor-infiltrating CD8+ Cells.
Time frame: Day of surgery: day 8-10
This will be assessed by the increase in the total number of tumor-infiltrating CD8+ T cells in the resected, recurrent CRC lesions (measured as the ratio between the CD8 mRNA message and the expression of the housekeeping gene HPRT), comparing Arm A and Arm B.
1 secondary outcome
Treatment Related Adverse Events
Time frame: 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2023.
- 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.
Amer H Zureikat, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Chemokin Modulatory Regimen (5 MU/m2), Chemokin Modulatory Regimen (10 MU/m2) and Chemokin Modulatory Regimen (20 MU/m2) in people with Colorectal Cancer and Colorectal Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
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 17 inclusion and 12 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: stopped early, as of the sponsor's last update on 27 Oct 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 9 Sep 2020). 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 the Number of Tumor-infiltrating CD8+ Cells. (time frame: Day of surgery: day 8-10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2023.