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

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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:

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

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:

Haslen

Midle name:

Hassiul

Last name:

Caceres Lavernia

Medical Specialty :

First Degree Specialist in Oncology

Affiliation:

Hermanos Ameijeiras Clinical Surgical Hospital (HHA)

Postal address:

San Lazaro nro 701 corner Belascoain. Centro Habana

City:

Havana

País:

Cuba

Zip Code:

10300

Telephone:

+53-78761436

Email address:

hassiul1978@gmail.com

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:

Havana, National Institute of Oncology and Radiobiology (INOR), Yoana Flores Perez, MD. First Degree Specialist in Oncology

Matanzas, Faustino Perez Clinical-Surgical Hospital, Kirenia Camacho Sosa, MD. Second Degree Specialist in 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:

01/07/2021

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:

Lung Cancer

Health condition(s) code:

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intervention(s):

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.

Intervention code:

Immunotherapy, Active

Epidermal Growth Factor

Protein-Tyrosine Kinases

Gefitinib

Cyclophosphamide

Injections, Intramuscular

Administration, Intravenous

Administration, Oral

Intervention keyword:

CIMAvax-EGF, osimertinib

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):

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.

Key secondary outcomes:

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.

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:

None

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.

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:

2

Target sample size:

20

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:

Orestes

Last Name:

Santos Morales

Specialty:

Second degree Specialist in Pharmacology

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

216 street cornrer 15, Playa

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

+53-72143144

Email :

orestesm@cim.sld.cu

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:

Haslen

Last Name:

Caceres Lavernia

Specialty:

First degree specialist in Oncology

Affiliation:

Hermanos Ameijeiras Clinical Surgical Hospital (HHA)

Postal Address:

San Lazaro street 701 corner Belascoain.

City:

Havana

País:

Cuba

Zip Code:

10300

Telephone:

+53-78761436

Email :

hassiul1978@gmail.com

Research Ethics Committees

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

Name of Research Ethics Committees:

Hermanos Ameijeiras Clinical Surgical Hospital (HHA)

National Institute of Oncology and Radiobiology (INOR)

Faustino Perez Clinical-Surgical Hospital

Status of evaluation:

In review

Status of evaluation date of Ethic Committee:

07/04/2021

Postal address of Ethic Committee :

San Lazaro street 701 corner Belascoain, Centro Habana, Havana ZC 10300, Cuba

29 street corner F. Vedado, Plaza, Havana, ZC 10400, Cuba

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

Telephone:

+53-78761000

+53-78322578

+53-45247016

Correo electrónico:

direccion@hha.sld.cu

docenciainor@inor.sld.cu

bibliotfaustinop.mtz@infomed.sld.cu

About study completion

Section to complete the data related to the study completion.

Study completion date:

31/07/2024

Date of available results:

31/12/2024

Date of first publication:

31/03/2025

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:

RPCEC00000371

Date of Registration in Primary Registry:

22/05/2021

Record Verification Date:

2021/05/22

Next update date:

2022/05/22

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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

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