Safety and efficacy of CIMAvax®-EGF in combination with tyrosine kinase inhibitors in patients with advanced stage Non-Small Cell Lung Cancer and EGFR mutations

• Register: RPCEC
• Last refreshed on: 21 June 2021
• Main ID: RPCEC00000371
• Date of registration: 22/05/2021
• Prospective Registration: Yes
• Primary sponsor: Center of Molecular Immunology (CIM)
• Public title: Safety and efficacy of CIMAvax®-EGF in combination with tyrosine kinase inhibitors in patients with advanced stage Non-Small Cell Lung Cancer and EGFR mutations
• Scientific title: Evaluation of the safety and efficacy of CIMAvax®-EGF in combination with tyrosine kinase inhibitors vs monotherapy with tyrosine kinase inhibitors as treatment in patients with advanced stage Non-Small Cell Lung Cancer and EGFR mutations
• Date of first enrolment: 01/07/2021
• Target sample size: 20
• Recruitment status: Pending
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000371-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Open. Control group: Active. Assignment: Parallel. Purpose: Treatment
• Phase: 2

Countries of recruitment

Cuba

Contacts

• Name: Orestes Santos Morales
• Affiliation: Center of Molecular Immunology (CIM)

• Name: Haslen Caceres Lavernia
• Affiliation: Hermanos Ameijeiras Clinical Surgical Hospital (HHA)

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients with cytological / histological confirmation of lung cancer in advanced stages, carriers of EGFR mutations.
2. Patients of any sex and age greater than or equal to 18 years.
3. Patients who have signed the informed consent for the research.
4. Patients with general clinical status according to the ECOG scale of 0 to 2.
5. Patients with a life expectancy equal to or greater than 6 months.
6. Patients who have functioning organs defined by the following parameters:
. Hemoglobin =90 g / L
. Total leukocyte count = 3.0 x 109 / L
. Absolute neutrophil count =1.5 x 109 / L
. Platelet count =100 x 109 / L
. Total bilirubin: Within normal limits.
. TGP and TGO: 2.5 times the institutional upper normal limit.
. Glycemia: Within normal limits for each institution.
. Creatinine: 2.0 times the institutional upper normal limit.
7. Life expectancy of at least 6 months
Exclusion criteria: 1. Patients with uncontrolled intercurrent diseases that include, but are not limited to: active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and psychiatric diseases that imply the incompetence of the subject.
2. Patients with autoimmune diseases or decompensated chronic diseases.
3. Patients with acute allergic conditions or history of severe allergic reactions.
4. Patients with brain metastases or other primary neoplastic lesion.
5. Patients with a previous history of demyelinating or inflammatory diseases of the CNS or peripheral.
6. Patients with other malignancy in the previous 5 years, except skin cancer (not melanoma).
7. Patients receiving another investigational product.
8. Pregnant or lactating patients.
9. Patients of childbearing potential who are not using an adequate method of contraception (intrauterine devices, hormonal contraceptives, barrier methods or tubal ligation).
10. Patients with known positive serology for Hepatitis B, C or HIV.
11. Patients with known hypersensitivity to any component of CIMAvax®-EGF or to the molecule of tyrosine kinase inhibitors.
12. Patients with hereditary galactose intolerance, total lactase deficiency, or glucose or galactose absorption problems.

Age minimum: 18 years
Age maximum: None
Gender: Male/Female

Health Condition(s) or Problem(s) studied

Bronchial Neoplasms

Carcinoma, Bronchogenic

Carcinoma, Non-Small-Cell Lung

Lung Cancer

Lung Diseases

Lung Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Intervention(s)

Administration, Intravenous

Administration, Oral

CIMAvax-EGF,
osimertinib

Cyclophosphamide

Epidermal Growth Factor

Experimental group: Cimavax-EGF. 2.4 mg per dose. The first 4 doses will be administered every 14 days and the remaining every 28 days, combined with tyrosine kinase inhibitors (gefitinib 250 mg or osimertinib 80 mg), 1 tablet orally once a day until one year of treatment (15 doses of Cimavax-EGF ), or loss of clinical benefit at the discretion of the investigator, or appearance of unacceptable toxicity. CIMAvax-EGF will be administered intramuscularly divided into 4 subdoses, equivalent to 0.6 mg of EGF at each site of inoculation (both deltoid regions and both glutes). Prior to receiving the first dose of the vaccine (72 hours), patients will receive a single dose of cyclophosphamide (CMF) 200 mg / m2 intravenously.
Control group: Tyrosine kinase inhibitors (gefitinib 250 mg or osimertinib 80 mg), 1 tablet orally once a day for one year of treatment, or loss of clinical benefit at the discretion of the investigator or unacceptable toxicity.

Gefitinib

Immunotherapy, Active

Injections, Intramuscular

Protein-Tyrosine Kinases

Primary Outcome(s)

Percentage of individuals with serious adverse events related to the use of CIMAvax® in combination with tyrosine kinase inhibitors (Percentage of patients with adverse events whose severity is classified as serious and whose causal relationship is definite, highly probable, probable or possible) . Measurement time: Weeks 0,2,4,6,10,14,18,22,26,30,34,38,42,46,50.

Secondary Outcome(s)

1. Adverse events-AE (Type of AE (according to CTC version 4.0 nomenclature), AE duration (Difference between AE start and end date), AE intensity (mild, moderate and severe), AE severity (It will be evaluated according to the serious / non-serious categories), attitude towards the study drug (1. No change, 2. Dose modification, 3. Temporary interruption or 4. Definitive interruption), AE result (Recovered, Improved, Persists , Sequelae), causal relationship of AE (Definitive, Very Probable, Probable, Possible, Not related, Unknown) Measurement time: Weeks 0,2,4,6,10,14,18,22,26,30,34 , 38,42,46,50)
2. Progression Free Survival (Time from randomization of the patient in the study to progression or death of the patient). Measurement time: Every 3 months for 1 year.
3. Overall Survival (Time from patient randomization in the study to death or date of latest news). Measurement time: Monthly for 1 year.
4. Objective response (According to RECIST criteria version 1.1 classified as Complete response, Partial response, stable disease, disease in progression). Measurement time: every 3 months for one year).
5. Quality of life (It will be measured through the EORTC surveys validated for this disease (QLQ-C30 and QLQ-LC13), in addition to the evaluation of the patient's Performance Status at each indicated moment. Measurement time: every three months for 1 year.
6. Serum EGF concentration (It will be measured in pg / mL using the ultramicro-ELISA system for the quantification of EGF (TECNOSUMA, CUBA). Measurement time: Day 0, Day 70, month 6, 9 and 12 and at the time of progression.
7. Inhibition of EGFR phosphorylation: (The EGFR phosphorylation fraction at a given moment of time will be measured in% compared to the initial time of the patient (100% phosphorylation) using the western blot technique. Measurement time: Day 0, Day 70, month 6, 9 and 12 and at the time of progression).
8. Antibody response against EGF (Based on the antibody response against EGF measured by ELISA studies, patients can be classified into: responders and non-responders (The criteria for their final evaluation will be: Responders: When 84 days after initiation the treatment, the optical density values are at least two times higher than that obtained pre-treatment and the titer is at least twice the pre-treatment (titer greater than or equal to 1: 4000), Non-responders: When at 84 days after starting the treatment, the optical density values are NOT at least two times higher than those obtained pre-treatment and the titer is NOT at least twice that of the pre-treatment (titer less than 1: 4000). Measurement time: Day 0, 70, 84, month 6, 9 and 12 and at the time of progression)
9. Levels of lymphocyte subpopulations (using the flow cytometry technique, the frequency (%) of cell subpopulations (CD4 +, CD8 + T cells, regulatory T cells and naive T cells) will be determined. Measurement time: Day 0, D 70, month 6, 9 and 12 and at the time of progression.
10. Inflammatory cell infiltrate (using standard techniques for determining platelet, neutrophil and lymphocyte levels, the number of cells per field will be determined and the neutrophil / lymphocyte (NLR) and platelet / lymphocyte (PLR) ratio will be calculated. Measurement time: before treatment and at the time of tumor progression, which is measured at 3,6,9 and 12 months or in the event of any suspicion that occurs outside the proposed evaluation scheme.
11. Levels of inflammatory cytokines (using the luminex technique, the cytokine pattern (TGF alpha, HB-EGF, HGF, IL-4, IL-6, IL-8, CRP) will be determined. Measurement time: Day 0, D70 , month 6, 9 and 12 and at the time of progression measured at 3,6,9 and 12 months or in the event of any suspicion that arises outside the proposed evaluation scheme).
12. Profile of tumor mutations. Measurement time: before treatment and at the time of tumor progression, which is measured at 3,6,9 and 12 months or in the event of any suspicion that occurs outside the proposed evaluation scheme.
13. PD-L1 expression level: It will be measured in% by applying the IHC technique, it is classified as =1 or <1. Measurement time: before treatment and at the time of tumor progression, which is measured at 3,6,9 and 12 months or in the event of any suspicion that occurs outside the proposed evaluation scheme.

Secondary ID(s)

Not applicable

Source(s) of Monetary Support

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

Secondary Sponsor(s)

Not applicable

Ethics review

Status: In review
Approval date: 07/04/2021
Contact:

[e-mail]

[e-mail]

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[e-mail]

Status: In review
Approval date: 07/04/2021
Contact:

[e-mail]

[e-mail]

[phone]

[e-mail]

Status: In review
Approval date: 07/04/2021
Contact:

[e-mail]

[e-mail]

[phone]

[e-mail]

Results

• Date Posted: 31/12/2024
• Date Completed: 31/12/2024