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

NCT02615574 | Withdrawn Phase 2 DMC

• 1 other identifier: 15-023
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• overall survival

  up to 36 months

Secondary Outcomes (2)

• immune-related Overall Response Rate (irORR)

  up to 36 months

• immune-related Progression-Free Survival (irPFS)

  up to 36 months

Other Outcomes (2)

• Changes of CD8+ tumor infiltrating lymphocytes (CTLs)

  up to 4 months

• Changes of tumor microenvironment

  up to 4 months

Study Arms (1)

αDC1 vaccine + CKM

EXPERIMENTAL

all subjects enrolled in study

Biological: αDC1 vaccine; Drug: CKM

Interventions

αDC1 vaccine BIOLOGICAL

Subjects will receive one cycle of CKM alone followed by three cycles of vaccine + CKM.

Also known as: alpha-type-1-polarized dendritic cell vaccine

αDC1 vaccine + CKM

CKM DRUG

Subjects will receive one cycle of CKM alone followed by three cycles of vaccine + CKM.

Also known as: celecoxib (Celebrex®), Interferon-α2b (IFN), rintatolimod (Ampligen®)

αDC1 vaccine + CKM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pawel Kalinski: lead

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Celecoxib; Introns; poly(I).poly(c12,U)

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes

Study Officials

• James J Lee, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: November 26, 2015
• Study Start: March 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 26, 2017

Record last verified: 2017-09

Locations

US (1)