Randomized Trial With Dendritic Cells in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The different alternatives used since 1996 to treat metastatic colorectal cancer (MCRC) have increased the mean survival of these patients. This outstanding advance is due to the extended indications for resection of hepatic metastases and to the use of new chemotherapeutic drugs (fluoropyrimidine, irinotecan and oxaliplatin) and monoclonal antibodies (bevacizumab, cetuximab and panitumumab). However, none of these treatments is curative and the majority of patients are overwhelmed by the illness. The first line of treatment for MCRC is FOLFOX and the second, irinotecan plus cetuximab for patients with wild type KRAS gene (60%) with a 30% responses, and bevacizumab plus irinotecan with a 5-10% of responses, in patients with mutated KRAS (40%). A treatment with autologous dendritic cells (DCs) pulsed with autologous tumour antigens is proposed as a third line of therapy. A randomized phase II trial would be performed, by selecting two groups of patients, one of them would be treated with the best supportive treatment and the other with DCs plus the best supportive treatment. The aim of the study would be to analyze the outcome after 4 months of treatment. In patients treated with DCs, IFN-γ spot forming cells and proliferative responses would be determined pre and post treatment in lymphocytes stimulated with autologous DCs pulsed with autologous tumour antigens. Pre and post treatment serum levels of IFN-γ, TNF-α, TGF-β e IL-12, would also be measured.

Official Title
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Randomized Phase II Trial in Patients With Progressive Stage IV Colorectal Cancer to Two Lines of Chemotherapy, in Order to Compare the Best Supportive Treatment Versus Treatment With Dendritic Cells Plus the Best Supportive Treatment

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Dendritic Cell Vaccine
* Other: Supportive treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years. Capacity of understanding and signing the informed consent and to undergo the study procedures. Previously treated with 2 lines of chemotherapy. ECOG <= 2. Adequate renal, hepatic and bone marrow function Confirmed diagnosis of colorectal cancer with hepatic metastasis, suitable for biopsy. Availability of tumor tissue, for maturing dendritic cells RECIST.1 criteria Exclusion Criteria: Clinically relevant diseases or infections (HBV, HCV, HIV). Pregnant or breast feeding women. Immunosuppressant treatment. Concurrent cancer, with the exceptions allowed by the principal investigator (PI).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dendritic Cells Vaccine<br>Dendritic Cells Vaccine after 2 lines of chemotherapy | Drug: Dendritic Cell Vaccine<br>* Vaccination with autologous dendritic cells loaded with autologous tumor antigens<br>|
| Other: Supportive treatment<br>Supportive treatment after 2 lines of chemotherapy | Other: Supportive treatment<br>* Supportive treatment after progression of the illness after 2 lines of chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Neoplasms, Dendritic Cells