Metastatic colorectal cancer, left-sided, unresectable
Conditions
Interventions
CIMAvax-EGF® group (Experimental): CIMAvax-EGF® therapeutic vaccine (2.4 mg, IM) + FOLFOX (FOLFOX4, FOLFOX6, or mFOLFOX6) + Bevacizumab for 12 treatment cycles, every 15 days for 24 weeks.
FOLFOX + Be
Drug Therapy
Antineoplastic Agents
Administration, Intravenous
Bevacizumab
Oxaliplatin
Leucovorin
FOLFOX, CIMAvax-EGF
Sponsors
Center of Molecular Immunology (CIM)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients who provide written informed consent 2. Patients who meet the diagnostic criteria. 3. Patients of either sex, between 18 and 75 years of age 4. Patients with metastatic disease, with at least one measurable metastatic lesion according to the Response Evaluation Criteria in Solid Tumors RECIST v 1.1 5. Tumor status of KRAS wild-type, confirmed by histology and/or liquid biopsy. 6. ECOG clinical status between 0 and 2 7. Life expectancy of at least three months 8. Normal hematologic, renal, hepatic, metabolic, and coagulation function as defined by: - Hemoglobin = 90 g/L (patients with lower Hb levels should be transfused prior to enrollment) - Total Leukocyte Count = 3.0 x 109/L - Absolute Neutrophil Count = 1.5 x 109/L - Platelet Count = 100 x 109/L - Bilirubin up to the upper limit of normal. - SGPT and SGOT: up to = 1.5 times the institution's upper limit of normal, or 50 mL/min/1.73 m2 for patients with creatinine levels above the institution's normal value.
Exclusion criteria
Exclusion criteria: 1. Have received prior chemotherapy or other systemic anticancer therapy for the treatment of metastatic colorectal carcinoma. 2. Have received prior chemotherapy for the primary tumor within six months prior to starting treatment. 3. History of central nervous system (CNS) metastases. 4. Prior treatment with bevacizumab or epidermal growth factor receptor (EGFR) inhibitors. 5. Patients with acute, chronic, or decompensated inflammatory diseases, including, but not limited to: clinically significant cardiac disease, clinically significant peripheral sensory neuropathy, active inflammatory bowel disease, recent active or uncontrolled gastroduodenal ulcer, history of interstitial lung disease, recent pulmonary embolism, deep vein thrombosis or other significant venous event, bleeding diathesis, and/or preexisting coagulopathy, with the exception of well-controlled anticoagulant therapy. 6. Major surgical procedure performed within the previous three months, open biopsy, or significant traumatic injury that has not yet recovered from previous major surgery. 7. Known or suspected allergy or hypersensitivity to any component of chemotherapy or the investigational product. 8. Pregnant or breastfeeding women. 9. Patients of childbearing potential who refuse to use adequate contraceptive methods (intrauterine devices, barrier methods or tubal ligation, hormonal methods).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Progression-free survival (Time from randomization until date of disease progression or death from any cause). Measurement time: every 3 months, for a period of 3 years until progression. 2. Adverse Events-AE (Occurrence of any AE (Yes, No), Type of AE (It will be classified according to the classification established by CTCAE v5.0), Duration of the AE (Time from the onset and the end of the adverse event), Intensity of the AE (It will be assessed according to the criteria established by the CTCAE v5.0 as 1. Mild, 2. Moderate, and 3. Severe), Causal relationship (1. Definite, 2. Very probable, 3. Probable, 4. Possible, 5. Unrelated, 6. Unknown), Severity (Severe/serious, Non-serious/non-serious), Treatment response (1. No change, 2. Dose modification, 3. Temporary interruption, or 4. Permanent discontinuation), Outcome of the AE (1. Recovered, 2. Improved, 3. Persistent, or 4. Sequelae.)). Measurement time: From randomization until 3 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival (Time from randomization until death from any cause. If the patient's death is uncertain, the time elapsed until the date the last patient update is recorded in the medical record will be recorded). Measurement time: Every 3 months, for a period of 3 years. 2. Objective response (RECIST 1.1 criteria, which subclassifies objective response into: a) complete response; b) partial remission; c) stable disease; and d) progressive disease). Measurement time: 3 months, 6 months, 12 months, 18 months, 24 months, and progression. 3. EGF-R expression. This refers to the tissue expression of the protein epidermal growth factor receptor, determined by immunohistochemical technique on formaldehyde-fixed, paraffin-embedded (FFEP) tissue blocks in tumor tissue from patients using colonoscopy. Scale: a) Negative, b) Positive +, c) Positive ++, and d) Positive +++). Measurement time: At baseline. 4. KRAS mutation status (Type of anomalous variant of the transcription factor KRAS, a protein responsible for the phosphorylation of several intracellular signal transduction pathways relevant to cancer, determined by molecular biology techniques from liquid biopsies obtained from peripheral blood and measured as a) Mutated, b) Not mutated). Measurement time: At baseline. 5. Serum EGF concentration (Refers to the concentration of the protein called epidermal growth factor, determined by ultramicroanalytical ELISA technology, in the serum of patients from whole blood without anticoagulants). Measurement time: At baseline, 6 months, 12 months, 18 months, 24 months, and at the time of progression. 6. Anti-EGF antibody concentration (Refers to the concentration of IgG class antibodies with high affinity for EGF determined by microanalytical ELISA technology, in patient serum from whole blood with EDTA anticoagulant, expressed as the positivity of the assay on diluted samples). Scale: Semiquantitative based on anti-EGF IgG antibody titers (1/2000, 1/4000, 1/8000, 1/16000, 1/ | — |
Countries
Cuba
Contacts
Public ContactGeidy Lorenzo Monteagudo
Center of Molecular Immunology (CIM)
Outcome results
None listed