Efficacy and safety of the monoclonal antibody nimotuzumab plus FOLFOX vs. FOLFOX as first-line treatment of patients with unresectable, left-sided, metastatic colorectal cancer. Phase I/II

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Secondary indentifying numbers:

Not applicable

Issuing authority of the secondary identifying numbers:

Not applicable

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM), Cuban Ministry of Public Health (MINSAP)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Reference number:

In process

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Ramon

Midle name:

Alberto

Last name:

Ortiz Carrodeguas

Medical Specialty :

First degree specialist in Oncology

Affiliation:

“Celestino Hernandez Robau” University Hospital

Postal address:

Cuba street 564 b/ Barcelona and Hospital, Santa Clara

City:

Villa Clara

Country:

Cuba

Zip Code:

50100

Telephone:

+53-42271202

+53-42279442

Email address:

raortizcarrodeguas@gmail.com [1]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Matanzas,“Faustino Perez” Hospital, Mileidys Santa Cruz More MD, First degree specialist in Clinical Oncology

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Pending

Date of first enrollment:

01/09/2025

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Metastatic colorectal cancer, left-sided, unresectable

Health condition(s) code:

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Rectal Diseases

Colonic Diseases

Intestinal Diseases

Gastrointestinal Diseases

Digestive System Diseases

Intervention(s):

Nimotuzumab group (experimental): Monoclonal antibody nimotuzumab (200 mg, intravenously) + FOLFOX (FOLFOX4, FOLFOX6, or mFOLFOX6) for 12 treatment cycles, every 15 days for 24 weeks. FOLFOX group (control): FOLFOX (FOLFOX4, FOLFOX6, or mFOLFOX6) for 12 treatment cycles, every 15 days for 24 weeks. FOLFOX4 (Oxaliplatin 85 mg/m2 IV over 2 hours on day 1 + Leucovorin 200 mg/m2 IV over 2 hours on days 1 and 2 + 5-FU 400 mg/m2 IV over 2 hours on days 1 and 2 followed by 600 mg/m2 IV infusion over 22-24 hours on days 1 and 2) FOLFOX6 (Oxaliplatin 100 mg/m2 IV over 2 hours on day 1 + Leucovorin 200 mg/m2 IV on days 1 and 2 + 5-FU 400 mg/m2 IV bolus on day 1 followed by 1200 mg/m2 IV daily, infusion over 22-24 hours on days 1 and 2 (total 2400 mg/m2 over 46-48 hours) mFOLFOX6 (Oxaliplatin 85 mg/m2 IV over 2 hours on day 1 + Leucovorin 400 mg/m2 IV over 2 hours on day 1 + 5-FU 400 mg/m2 IV bolus on day 1 followed by 1200 mg/m2 IV daily, 22-24 hour infusion on day 1 and 2 (total 2400 mg/m2 over 46-48 hours)

Intervention code:

Antibodies, Monoclonal, Humanized

Antibodies, Monoclonal

Drug Therapy

Oxaliplatin

Leucovorin

Antineoplastic Agents

Administration, Intravenous

Intervention keyword:

Nimotuzumab, FOLFOX

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

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, measured from the patient's inclusion in the trial. 2. Adverse Events- AE (Occurrence of any AE (Yes, No), Type of AE (It will be classified according to the classification established by the CTC (Common Toxicity Criteria) version 5.0 of the US National Cancer Institute), 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 CTC (Common Toxicity Criteria) version 5.0 of the US National Cancer Institute 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.

Key secondary outcomes:

1. Overall survival (Time measured from the date of inclusion in the study to the date of death. 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: From inclusion in the trial to death or last contact. 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: (D 0) before the start of treatment. 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: Before the start of treatment.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

75 years

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. Clinical status according to ECOG between 0 and 2 6. Life expectancy of at least three months 7. Normal hematological, renal, hepatic, metabolic, and coagulation function defined by: - Hemoglobin ≥ 90 g/L (patients with lower Hb levels should be transfused prior to inclusion) - 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 <5 times the institution's upper limit of normal, if liver metastasis is known. - Alkaline phosphatase ≥2.5 times the upper limit of normal - Creatinine: Within normal limits for each institution, or creatinine clearance >50 mL/min/1.73 m2 for patients with creatinine levels above the institution's normal.

Exclusion criteria:

1. Having received prior chemotherapy or other systemic anticancer therapy for the treatment of metastatic colorectal carcinoma. 2. Having 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 epidermal growth factor receptor (EGFR) inhibitors. 5. Patients with acute infectious, 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 three months prior, open biopsy, or significant traumatic injury that has not yet recovered from prior major surgery. 7. Known or suspected allergy or hypersensitivity to any component of the chemotherapy or the investigational product. 8. Pregnant or breastfeeding women. 9. Patients of childbearing age who do not agree to use adequate contraceptive methods (intrauterine devices, barrier methods or tubal ligation, hormonal methods).

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Open

Control group:

Active

Study design:

Parallel

Phase:

1-2

Target sample size:

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Geidy

Last Name:

Lorenzo Monteagudo

Specialty:

Ph. D. In Pharmaceutical Sciences

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

Calle 216 Esquina 15, Atabey, Playa.

City:

Havana

Country:

Cuba

Zip Code:

16040

Telephone:

+53-72717933 ext 3391

Email :

geydi@cim.sld.cu [2]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Ramon

Middle Name:

Alberto

Last Name:

Ortiz Carrodeguas

Specialty:

First degree specialist in Oncology

Affiliation:

“Celestino Hernandez Robau” University Hospital

Postal Address:

Cuba street 564 b/ Barcelona and Hospital, Santa Clara

City:

Villa Clara

Country:

Cuba

Zip Code:

50100

Telephone:

+53-42 271202, +53- 42279442

Email :

raortizcarrodeguas@gmail.com [1]

Research Ethics Committees

Section to complete the data related to the review ethics committees.

Name of Research Ethics Committees:

"Celestino Hernandez Robau" University Hospital

Comandante Faustino Perez Hernandez surgical clinical university hospital

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

07/01/2025

11/03/2025

Postal address of Ethic Committee :

Cuba No. 564 entre Hospital y Barcelona, Santa Clara, Villa Clara. Cuba

Carretera Central Km 101. ZC: 40100, Matanzas. Cuba

Telephone:

+ 53-56096863

+53-45247016

Email:

direccionhchr@infomed.sld.cu

bibliotfaustinop.mtz@infomed.sld.cu

About study completion

Section to complete the data related to the study completion.

Study completion date:

01/09/2030

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000461

Date of Registration in Primary Registry:

12/08/2025

Record Verification Date:

2025/08/12

Next update date:

2026/08/12

Link to the spanish version:

Click here [3]