Vaccination Against MSI Colorectal Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/IIa Study of Immunization With Frameshift Peptides Administered With Montanide® ISA-51 VG in Patients With Advanced MSI-H Colorectal Cancer|
- immune response against FSP peptides [ Time Frame: every two weeks ] [ Designated as safety issue: No ]A positive immune response is defined as positive delayed-type hypersensitivity (DTH) response against at least one of the peptides or a humoral (ELISA for the detection of FSP-specific IgG/IgM/IgA) and/or CD8 and/or CD4 cellular (IFN gamma ELISpot for the detection of FSP-specific T cells) immune response exceeding the assay specific cut-off values for a positive response against at least one of the three peptides
- Tumor response [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]Tumor response is assessed by CT or MRI scans according to RECIST.
- safety [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]Safety as assessed by number and severity of adverse events categorized according to CTC criteria v4.0 and the probability of the induction of immune tolerance. Immune tolerance is defined as significant and sustained decline of antigen-specific cellular immune responses after vaccination compared to the antigen-specific cellular immune response measured before vaccination , as assessed by Interferon-gamma (IFN-g) ELISpot using assay-specific cut-off values.
|Study Start Date:||August 2011|
|Study Completion Date:||May 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: FSP peptides
Vaccination with three FSP peptides
Biological: FSP peptides
100 ug of each FSP (TAF1B(-1), HT001(-1) and AIM2(-1), weekly for 4 consecutive weeks and repeated every four weeks up to a total of 3 cycles.
The present study is initiated to evaluate vaccination with MSI-specific FSPs in patients with MSI-H colorectal cancer. Specifically, the present study aims at the following questions:
- Evaluation of potential toxicity of the FSP AIM2(-1), HT001(-1), TAF1B(-1)
- Evaluation of the immune response in patients with advanced MSI-H colorectal cancer before vaccination and after vaccination with the FSP AIM2(-1), HT001(-1), TAF1B(-1)
In this context, the present study shall demonstrate whether application of FSP in a vaccination approach is associated with the induction of peptide-related toxicity. Hence, the study marks the first step towards the application of FSP in humans, as it provides information on the safety of FSP as vaccination agents for the first time. Moreover, the study shall provide initial information, whether vaccination with FSP can induce FSP-specific immune responses in patients with MSI-H colorectal cancer. Thus, it shall provide information, whether FSPs AIM2(-1), HT001(-1), and TAF1B(-1) have the potential to elicit peptide-specific immune responses and therefore represent suitable targets for the induction of tumor antigen-specific immune responses in patients with MSI-H tumors.
The present study marks an important milestone towards a potential application of MSI-specific FSP as therapeutic agents in the management of patients with MSI-H tumors, particularly patients with MSI-H colorectal cancer. Long-term goal of this approach is to develop novel tools for (1) the palliative and/or adjuvant therapy of patients with advanced MSI-H colorectal cancer and (2) the preventive application of FSPs in mutation carriers of the HNPCC/Lynch syndrome.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01461148
|Frankfurt/Main, Germany, 60488|
|Principal Investigator:||Elke Jäger, Prof. Dr.||Krankenhaus Nordwest Frankfurt|