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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Biological: αDC1 vaccine; Drug: CKM

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	up to 36 months

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of CD8+ tumor infiltrating lymphocytes (CTLs)	Changes in CD8+ CTLs in paired tumor tissues collected at pre- and post-treatment.	up to 4 months
Changes of tumor microenvironment	Changes of tumor microenvironment in paired tumor tissues collected at pre- and post-treatment.	up to 4 months

Collaborators and Investigators

• Sponsor: Pawel Kalinski
• Investigators: Principal Investigator: James J Lee, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): November 26, 2015

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Immunologic Factors; Cyclooxygenase 2 Inhibitors; Interferons; Vaccines; Celecoxib; poly(I).poly(c12,U)
• Other Study ID Numbers: 15-023