Colorectal cancer large bowel and rectal cancer
Conditions
Interventions
Eligible patients will receive 2 vaccinations consisting of 9 synthetic long
peptides, 300 µg per peptide, emulsified in DMSO / 20 mM PBS / Montanide ISA 51
20/30/50 v/v/v by subcutaneous injection
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Willing and able to comply with the protocol and to provide informed consent in accordance with institutional and regulatory guidelines - Patients must be 18 years or older. - Histological proven colorectal carcinoma - At least one month after last treatment - Life expectance of more than 6 months - Patients of child-bearing potential should test negative using a serum pregnancy test and agree to utilize effective contraception during the entire treatment and follow-up period of the study - Patients must be ambulatory, with an WHO performance status of 0 to 1 - Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; conditions should be discussed with the patient before registration in the trial - Baseline laboratory findings; haemoglobin > 6.0mmol/L, white blood cells (WBC) > 3,000 x 109/L, lymphocytes > 1,000 x 109/L, platelets > 100 x 109/L, HIV- and HBV-negative
Exclusion criteria
Exclusion criteria: - History of an autoimmune disease or other systemic intercurrent disease that might affect the immunocompetence of the patient, or patients receiving immunosuppressive therapy including transplant recipients - History of a second malignancy except curatively treated low-stage tumours with a histology that can be differentiated from colorectal cancer - Any condition that in the opinion of the investigator could interfere with the conduct of the study - Radiotherapy, chemotherapy or other potentially immunosuppressive therapy administered within 4 weeks prior to the enrolment visit - Receipt of another investigational product within the previous 4 weeks or at any time during the study period - Receipt of prior P53 directed immunotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety will be assessed during the whole study by collecting all adverse events according CTC version 3.0 (with a focus on administration site reactions), vital signs, blood-chemistry and haematological parameters. Immunogenicity will be assessed by an array of complementary immunological assays which focus on p53-specific T-cell proliferation, enumeration of circulating IFNγ-producing T-cells, Th1/Th2 cytokine production, and p53 protein recognition by circulating and vaccine-site-homing T-cells. However, the primary endpoint is determined by the directly ex-vivo detectable p53-specific CD4+ T-cell response and is defined by the percentage of CD3+CD4+ T cells that up-regulate the activation markers CD154 and CD137 upon stimulation with p53 antigen in freshly tested PBMC as measured by multiparameter flowcytometry. The immunological endpoint is successful if a combination of the p53-SLP vaccine combined with subcutaneous injection of IFN* is capable of inducing a directly ex-vivo detectable p53-specific CD4+ T-cell response in at least 70% of the vaccinated patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoint is successful if a combination of the p53-SLP vaccine combined with subcutaneous injection of interferon-alfa is capable of inducing a more pronounced Th1 response in the vaccinated patients. Th1 response is defined as the number of IFNγ producing T-cells in ELISPOT, the proportion of IFNγ producing cells in the total population of p53-specific T-cells measured by multiparameter flow cytometry, as well as the amount of IFNγ in the supernatant of proliferation assays. All which were low in our previous trial. | — |
Countries
Netherlands
Outcome results
None listed