Combined NGcGM3/VSSP and Nimotuzumab in advanced non-small cell lung cancer (NSCLC)

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:

Combined immunotherapy with the vaccine preparation NGcGM3/VSSP and the monoclonal antibody nimotuzumab, in patients with advanced non-small cell lung cancer (NSCLC)

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) 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)

Authorization date :

13/12/2017

Reference number:

05.011.16BC

Principal investigator

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

First name:

Soraida

Last name:

Acosta Brooks

Medical Specialty :

Second degree specialist in Internal Medicine

Affiliation:

"Saturnino Lora Torres" Provincial Teaching Surgical-Clinic Hospital

Postal address:

The Libertadores Avenue, between 4th and 6th

City:

Santiago de Cuba

País:

Cuba

Zip Code:

90100

Telephone:

+53-022626577

Email address:

soraida@medired.scu.sld.cu [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:

Santiago de Cuba, “Juan Bruno Zayas ” Hospital. Sahily Quintero Salcedo, MD. First degree specialist in Pneumology

Havana, “National Institute of Oncology and Radiobiology". Yoanna Ivette Flores Vega, MD. First degree specialist in Oncology

Research ethics committees:

Saturnino Lora, August 25, 2016

Juan Bruno Zayas, September 22, 2016

National Institute of Oncology and Radiobiology, October 7, 2016

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

30/04/2018

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:

Non Small Cell 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):

Group A (patients with + NGcGM3 expression): NGcGm3/VSSP vaccine (subcutaneous), dose of 900µg, the first 5 immunizations every 14 days and the following immunizations every 28 days, up to 24 months Group B (patients with + EGF-R expression) nimotuzumab AcM (intravenous) : 200 mg, the first 6 doses every 7 days, and the following every 14 days, up to 24 months Group C (+ NGcGM3 and + EGF-R expression), will receive the combination of both products, following the schemes provided for every product separately, starting with nimotuzumab and after 48 to 72 hours, the NGcGM3 / VSSP vaccine Patients may continue to receive treatment with the investigational product (s), at the discretion of the physician, until the onset of non-manageable toxicity or worsening of the general condition (ECOG≥3).

Intervention code:

G(M3) Ganglioside

Receptor, Epidermal Growth Factor

Antibodies, Monoclonal, Humanized

Gangliosides

Proteolipids

Antineoplastic Agents

Immunotherapy, Active

Adjuvants, Immunologic

Receptor, Epidermal Growth Factor

Antineoplastic Combined Chemotherapy Protocols

Antineoplastic Agents

Administration, Intravenous

Injections, Subcutaneous

Intervention keyword:

NGcGM3/VSSP, Nimotuzumab

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):

Overall Survival (Time from randomization-recruitment until death from any cause). Measuring time: 3, 6, 9, 12, 15, 18, 21, 24 months.

Key secondary outcomes:

Related to Security Adverse Events-AE. Measuring time: 3, 6, 9, 12, 15, 18, 21, 24 months. AE will be measured as: - Occurrence of any AE (Yes or No). - Duration AE (Difference of dates between the start and end AE). - Type AE: (Description AE according to CTCAE, 4.0). - Intensity AE (According to CTCAE, 4.0 as Mild, Moderate, Severe, Serious that Life-threatening or incapacitates the subject, Death). - serious AE (Serious or not serious) - Attitude towards the drug (Modification of the dose, temporary interruption, definitive interruption of the treatment). - Result AE (Recovered, improved, persists or leaves sequels). - Causal relationship (very probable, probable, possible, improbable, unrelated, non-assessable) - Treatment indicated (Treatment received by the patient for the submitted AE). Results of laboratory tests measured in numerical values (hemoglobin, leukogram with differential, CAN, platelet count, TGP, GOT, creatinine, glycemia, alkaline phosphatase, total bilirubin). Measurement time: at the beginning, every 3 months during the treatment. Prior to each cycle of chemotherapy (2nd line) Related to the effect: Objective response - OR (According to RECIST, classified as a partial response, stable disease or progressive disease). Measurement time: at the beginning, 3, 6, 9, 12, 15, 18, 21, 24 months. Progression-free survival-PFS (Time from the date of inclusion of each patient until date of progression). Measurement time: 24 months. Duration of the objective response (It will be measured using the RECIST). Measurement time: 24 months Immunological response measured as. - Response of IgM and IgG isotype antibodies against ganglioside NGcGM3 (Measurement: Ac title). Measurement time: at baseline, 3, 6 12 months. - Recognition and lytic capacity of IgM and IgG antibodies, induced by vaccination and directed to NGcGM3, on tumor lines expressing the ganglioside. [Measurement:%, greater than 20% cellular in the line that expresses the ganglioside (L1210)]. Measurement time: at baseline, 3, 6 12 months. - Serum concentration of EGF and EGF-R (pg/ml). Measurement time: at baseline, 3, 6 12 months.

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 confirmed diagnosis of NSCLC 2. Patients who consent to participate in the study by signing the informed consent model. 3. Patients older than 18 years. 4.Clinical and radiological documentation the evaluation of the response to the oncoespecific treatment of 1st line 5. Partial or stable response (RECIST), at the end of the first-line onco-specific treatment.6.Patients with + expression of EGF-R and / or NGcGM3 7.Patients with ECOG scale of Performance Status ≤ 2. 8.Life expectancy at least 6 month 9. Time from the end of first-line oncospecific therapy to inclusion, no longer than 2 months 10. Patients with normal functioning of organs and bone marrow defined by laboratory parameters - Hemoglobin >9 g/L, - White blood cell (WBC) count > 3000/ µL, - Neutrophils ≥ 1.5 x 109/L , - Platelet count ≥ 100,000 per µL, - Total bilirubin: in normal labs values, - AST and ALT ≤ 2.5 x upper limit of normal (ULN), - Serum creatinine in normal labs values, - Glycemia: in normal labs values

Exclusion criteria:

1.Patients with fertile age. 2. Pregnancy, lactation or puerperium. 3. Patients with history of severe allergy disease. 4. Patients who have been treated with NGcGm3/VSSP, nimotuzumab or some other EGF-R blocker. 5. Patients with descompensated chronic diseases. 6. patients with previous demyelinating and inflammatory diseases 7. Patients with previous malignancies, except carcinoma in situ of cervix or skin cancer (non-melanoma), correctly treated 8. Patients with acute or chronic infectious diseases 9. Patients with brain metastases.

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:

Non-randomized controlled trial

Masking:

Open

Control group:

Uncontrolled

Study design:

Parallel

Phase:

N/A

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:

Pedro

Middle Name:

Pablo

Last Name:

Guerra Chaviano

Specialty:

Master in Clinical Trials.

Affiliation:

National Coordinating Center of Clinical Trials (CENCEC)

Postal Address:

5ta A avenue. Betwen 60 & 62, Playa

City:

Havana

País:

Cuba

Zip Code:

11300

Telephone:

+53-72164224

Email :

pedrop@cencec.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:

Barbara

Last Name:

Wilkinson Brito

Specialty:

Bachelor of Pharmaceutical Sciences

Affiliation:

Center of Molecular Immunology

Postal Address:

216 y 15, Atabey, Playa

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

+53-72143144

Email :

wilkinson@cim.sld.cu [3]

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:

RPCEC00000270

Date of Registration in Primary Registry:

30/04/2018

Record Verification Date:

2020/12/21

Next update date:

2021/12/21

Link to the spanish version:

Click here [4]