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

INTERVENTION: Product Name: AUTOLOGOUS DENDRITIC CELLS Pharmaceutical Form: Solution for injection INN or Proposed INN: AUTOLOGOUS DENDRITIC CELLS Concentration unit: EID50/dose 50% Embryo Infective Dose/dose Concentration type: up to Concentration number: 25000000 CONDITION: STAGE IV COLORECTAL CANCER PROGRESSIVE TO TWO LINES OF CHEMOTHERAPY. MedDRA version: 13.1 Level: PT Classification code 10010035 Term: Colorectal cancer stage IV System Organ Class: 10029104 - Benign, malignant and unspecified neoplasms (incl cysts and polyps) PRIMARY OUTCOME: Main Objective: To increase time to disease progression and overall survival in patients with refractory colorectal cancer (CRC) after two lines of treatment (chemotherapy and biological agents), which would materialize 4 months after the patient's inclusion in the dendritic cell vaccination program. Primary endpoint(s): Progression-free survival (PFS): time from the date of inclusion to the date of radiological progression or death (whichever occurs first). Subjects who have not progressed while in the study and have not died while in the study will be censored at the last radiological evaluation date without evidence of progression. Subjects who discontinued treatment in the study before 4 months for any reason must be followed up every 8 weeks. Subjects who underwent surgery for metastases will not be censored at the date of surgery but will be followed as described in the study until progression is documented. If, for any reason, only the baseline CT scan is performed (subject withdrawal from the study or loss to follow-up), the subject will be censored on day +1 from the enrollment date. Secondary efficacy: Objective response rate (ORR): incidence of CR or PR according to the revised RECIST 1.1 criteria; Duration of response (DR): (calculated only for subjects with an objective response) time from the first objective response to radiological disease progression according to the revised RECIST 1.1 criteria. For subjects who respond but have not progressed, the duration of response will be censored at the last evaluable disease assessment date. Time to Response (THR): (calculated only for subjects who achieve an objective response) time elapsed from the date of enrollment to the date of the first objective response; Disease Control Rate (DCR): incidence of CR or PR or stable disease (SD). Subjects who prematurely discontinue the trial without undergoing a post-baseline tumor response assessment will be considered not to have disease control; Time to Treatment Failure (THF): time from enrollment to the date the decision was made to terminate the treatment phase, for any reason. For subjects still in the treatment phase at the time of analysis, time to treatment failure will be censored at the date of their last radiographic assessment during the study; Time to Progression (THP): time elapsed from the date of enrollment to the date of radiographic disease progression, according to the modified RECIST criteria. Subjects who do not meet the criteria for disease progression by the data analysis cutoff date will be censored at their last evaluable disease assessment date. Duration of stable illness (DSI): calculated only for subjects with EE as their best response during the treatment period, the time from enrollment to the date of the first observed disease progression or death due to disease progression (whichever occurs first). For subjects who do not progress while in the study or who die during the study for reasons other than disease progression, the duration of stable illness at the last evaluable disease assessment date will be censored. Overall survival (OS): time from the date of enrollment to the date of death. For subjects who have not died or who are lost to follow-up by the data analysis cutoff date, OS will be censored at the date of last contact. Secondary Objective: 1. To define an effective protocol for the treatment of patients with refractory MRC with dendritic cells loaded ex vivo with autologous tumor antigens; 2. To determine parameters for monitoring the immune response induced by dendritic cells. INCLUSION CRITERIA: Patients who meet all of the following criteria will be included in the study: 1. Obtaining written informed consent. 2. Confirmed histological diagnosis