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Sponsors and Collaborators: |
AlphaVax, Inc. Duke University |
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Information provided by: | AlphaVax, Inc. |
ClinicalTrials.gov Identifier: | NCT00529984 |
STUDY OBJECTIVES
Condition | Intervention | Phase |
---|---|---|
Colorectal Cancer Breast Cancer Lung Cancer Pancreatic Cancer |
Biological: AVX701 |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Phase I/II Study of Active Immunotherapy With CEA(6D)VRP Vaccine(AVX701)in Patients With Advanced or Metastatic Malignancies Expressing CEA |
Estimated Enrollment: | 24 |
Study Start Date: | September 2007 |
Estimated Study Completion Date: | September 2009 |
Estimated Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Cohort 1: Experimental |
Biological: AVX701
4 doses of AVX701 at 4e7 IU given at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease
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Cohort 2: Experimental |
Biological: AVX701
4 doses of AVX701 at 1e8 IU given at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease
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Cohort 3: Experimental |
Biological: AVX701
4 doses of AVX701 at 4e8 IU given at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease
|
Cohort 4: Experimental |
Biological: AVX701
4 doses of AVX701 given at the maximally tolerated dose at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease
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CEA represents an attractive target antigen for immunotherapy since it is over expressed in nearly all colorectal cancers and pancreatic cancers, and is also expressed by some lung and breast cancers, and uncommon tumors such as medullary thyroid cancer, but is not expressed in other cells of the body except for low-level expression in gastrointestinal epithelium [1]. That CEA is a potential target for T cell mediated immune responses in humans is demonstrated by the observation that CEA contains epitopes that may be recognized in an MHC restricted fashion by T cells [2-11]. Specifically, there is support for the existence of human cytolytic T cells (CTLs) that recognize CEA epitopes that bind to MHC molecules HLA- A2, A3, and A24. For the most part, these T cells have been generated by in vitro cultures using antigen-presenting cells pulsed with the epitope of interest to stimulate peripheral blood mononuclear cells. In addition, T cell lines have been generated after stimulation with CEA latex beads, CEA protein-pulsed plastic adherent peripheral blood mononuclear cells, or DCs sensitized with CEA RNA. T cells have also been generated from patients immunized with a vaccinia vector encoding CEA immunogen (discussed below). Using high-performance liquid chromatography mass-spectrometry-based approaches, HLA A2-presented peptides from CEA have been identified in primary gastrointestinal tumors [12]. Of the HLA A2 restricted epitopes of CEA, CAP-1, a nine amino acid sequence, has been shown to stimulate CTLs from cancer patients immunized with vaccinia-CEA. Cap-1(6D) is a peptide analog of CAP-1. Its sequence includes a heteroclitic (nonanchor position) mutation, resulting in an amino acid change from Asn to Asp, to enhance recognition by the T-cell receptor without any change in binding to HLA A2. Compared with the non mutated CAP-1 epitope, Cap-1(6D) has been shown to enhance the sensitization of CTLs by 100 to 1,000 times [3, 5, 13]. CTL lines could be elicited from peripheral blood mononuclear cells of healthy volunteers by in vitro sensitization to the Cap-1(6D) peptide but not to the CAP-1 peptide. These cell lines can lyse human tumor cells expressing endogenous CEA.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Michael Morse, M.D. | 919-681-3480 | michael.morse@duke.edu |
United States, North Carolina | |
Duke University Medical Center | Recruiting |
Durham, North Carolina, United States, 27710 |
Principal Investigator: | Michael Morse, M.D. | Duke University |
Responsible Party: | Duke University Medical Center ( Michael Morse, M.D., Chairman and Principal Investigator ) |
Study ID Numbers: | AVX701, P01 CA78673-04 |
Study First Received: | September 12, 2007 |
Last Updated: | November 7, 2008 |
ClinicalTrials.gov Identifier: | NCT00529984 |
Health Authority: | United States: Institutional Review Board |
CEA CEA-expressing malignancies Metastatic malignancies |
VRP Vaccine Alphavirus replicons Molecular therapeutics |
Thoracic Neoplasms Digestive System Neoplasms Skin Diseases Gastrointestinal Diseases Pancreatic Neoplasms Colonic Diseases Endocrine System Diseases Breast Neoplasms Intestinal Diseases Rectal Diseases Intestinal Neoplasms |
Digestive System Diseases Respiratory Tract Diseases Lung Neoplasms Lung Diseases Pancreatic Diseases Gastrointestinal Neoplasms Endocrinopathy Colorectal Neoplasms Breast Diseases Endocrine Gland Neoplasms |
Respiratory Tract Neoplasms Neoplasms Neoplasms by Site |