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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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2016 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Pawel Kalinski, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02615574
First received: November 24, 2015
Last updated: March 31, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Metastatic Colorectal Cancer
Biological: αDC1 vaccine
Drug: CKM
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • overall survival [ Time Frame: up to 36 months ]

Secondary Outcome Measures:
  • immune-related Overall Response Rate (irORR) [ Time Frame: up to 36 months ]
  • immune-related Progression-Free Survival (irPFS) [ Time Frame: up to 36 months ]

Other Outcome Measures:
  • Changes of CD8+ tumor infiltrating lymphocytes (CTLs) [ Time Frame: up to 4 months ]
    Changes in CD8+ CTLs in paired tumor tissues collected at pre- and post-treatment.

  • Changes of tumor microenvironment [ Time Frame: up to 4 months ]
    Changes of tumor microenvironment in paired tumor tissues collected at pre- and post-treatment.


Estimated Enrollment: 44
Study Start Date: March 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: αDC1 vaccine + CKM
all subjects enrolled in study
Biological: αDC1 vaccine
Subjects will receive one cycle of CKM alone followed by three cycles of vaccine + CKM.
Other Name: alpha-type-1-polarized dendritic cell vaccine
Drug: CKM
Subjects will receive one cycle of CKM alone followed by three cycles of vaccine + CKM.
Other Names:
  • celecoxib (Celebrex®)
  • Interferon-α2b (IFN)
  • rintatolimod (Ampligen®)

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02615574

Contacts
Contact: Natalie Streeter, RN 412-235-1276 streeternr@upmc.edu

Locations
United States, Pennsylvania
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Pawel Kalinski
Investigators
Principal Investigator: James J Lee, MD, PhD University of Pittsburgh
  More Information

Responsible Party: Pawel Kalinski, Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02615574     History of Changes
Other Study ID Numbers: 15-023
Study First Received: November 24, 2015
Last Updated: March 31, 2016

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Vaccines
Poly I-C
Interferons
poly(I).poly(c12,U)
Celecoxib
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on April 27, 2017