A Study of Type-1 Polarized Dendritic Cell (αDC1) Vaccine in Combination With Tumor-Selective Chemokine Modulation (Interferon-α2b, Rintatolimod, and Celecoxib) in Subjects With Chemo-Refractory Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The investigators hypothesize that the treatment of metastatic colorectal cancer (mCRC) patients with the combination of alpha-type-1-polarized dendritic cell (αDC1) vaccines and tumor-selective chemokine modulation (CKM) will promote the infiltration of vaccination-induced CD8+ CTLs to tumor lesions and subsequently tumor regression with improved patient survival.

Detailed Description
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Metastatic colorectal cancer is a major health concern in the United States, and the second leading cause of death due to cancer. The purpose of this trial is to see if the combination of the study vaccine and drugs in patients with this disease can prevent the growth of cancer and prevent new tumors from growing. The study drugs are a combination of celecoxib (Celebrex®), Interferon-α2b (IFN), and rintatolimod (Ampligen®), or CKM.

Official Title
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A Phase 2 Study of Type-1 Polarized Dendritic Cell (αDC1) Vaccine in Combination With Tumor-Selective Chemokine Modulation (Interferon-α2b, Rintatolimod, and Celecoxib) in Subjects With Chemo-Refractory Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Biological: αDC1 vaccine
* Drug: CKM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be age equal to 18 years or older. Be able to understand and be willing to sign a written informed consent document. Be HLA-A2 positive. Have mCRC that has been treated with currently approved standard therapies, including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Have at least 1 of the tumor sites that must be amenable to core needle biopsy and this may not be the site of disease used to measure antitumor response. Have measurable disease based on irRC. Have a performance status of ECOG 0 or 1.Have normal organ and marrow function as defined below: Platelet ≥ 75,000/µL Hemoglobin ≥ 9.0 g/dL Absolute Neutrophil Count (ANC) ≥ 1500/µL Creatinine < 1.5 x institutional upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels greater than 1.5 x 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) OR ≤ 5 x ULN for subjects with liver metastases Serum amylase and lipase within normal limits. Exclusion Criteria: Is currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Has active autoimmune disease or history of transplantation. Is a woman of child bearing potential (WOCBP) who are pregnant or nursing. Has a history of cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent. Subjects with a New York Heart Association classification of III or IV. Has a history of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years. Subjects with ulceration, bleeding or perforation in the lower bowel are not excluded. Has prior allergic reaction or hypersensitivity to celecoxib, or NSAIDs. Has an active infection requiring systemic therapy. Has significant ascites or pleural effusion requiring drainage for symptom relief. Has a known history of Human Immunodeficiency Virus (HIV). Has known active Hepatitis B or Hepatitis C infection. Has history of asthma, or other allergic-type reactions after taking aspirin or other NSAIDs. Has known serious hypersensitivity reactions to peg-interferon alfa-2b or interferon alfa-2b. Has autoimmune hepatitis. Has hepatic decompensation (Child-Pugh score > 6; = class B and C).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: αDC1 vaccine + CKM<br>all subjects enrolled in study | Biological: αDC1 vaccine<br>* Subjects will receive one cycle of CKM alone followed by three cycles of vaccine + CKM.<br>* Other names: alpha-type-1-polarized dendritic cell vaccine;Drug: CKM<br>* Subjects will receive one cycle of CKM alone followed by three cycles of vaccine + CKM.<br>* Other names: rintatolimod (Ampligen®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immune-related Overall Response Rate (irORR) |  | up to 36 months | 
| immune-related Progression-Free Survival (irPFS) |  | up to 36 months |