CENTAURO-6 Study

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:

Safety, immunogenicity and evidence of effect of vaccine candidate CIGB-247 in the treatment of hepatocellular carcinoma.

Secondary indentifying numbers:

IG/CIGB-247I/TS/1606

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB), in Havana.

Source(s) of monetary or material support:

Center for Genetic Engineering and Biotechnology (CIGB), Havana.

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:

Julio

Midle name:

Cesar

Last name:

Hernandez Perera

Medical Specialty :

Doctor of Medical Sciences, Specialist of 2nd degree in Internal Medicine.

Affiliation:

Center for Surgical Medical Research.

Postal address:

Calle 216 y 11b, Reparto Siboney, Playa

City:

Havana

Country:

Cuba

Zip Code:

12100

Telephone:

+53-78581000

Email address:

julio.hernandez@infomed.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:

Not applicable

Research ethics committees:

Center for Surgical Medical Research, December 12, 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:

03/04/2017

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:

Hepatocellular carcinoma

Health condition(s) code:

Liver Neoplasms

Carcinoma, Hepatocellular

Digestive System Neoplasms

Liver Diseases

Digestive System Diseases

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Intervention(s):

Group I (experimental): Antigen p64K-hVEGFKDR-(800 μg) + NAcGM3s / synthetic VSSP (200 μg) applied subcutaneously in the deltoid region. The first 8 weeks, the subjects will receive an immunization every week. Then, the subjects will receive re-immunizations every 28 days for 24 months. Group II (experimental): Antigen p64K-hVEGFKDR-(800 μg) + Aluminum phosphate (0.7 mg AL3 +) applied subcutaneously in the deltoid region. The first 8 weeks, the subjects will receive an immunization every 14 days. Then, the subjects will receive re-immunizations every 28 days for 24 months.

Intervention code:

Antigens

Vascular Endothelial Growth Factors

G(M3) Ganglioside

Immunotherapy, Active

Gangliosides

Proteolipids

N-Acetylneuraminic Acid

Adjuvants, Immunologic

Vaccines

Injections, Subcutaneous

Intervention keyword:

CIGB-247, Vaccine anti-VEGF, p64K-hVEGFKDR Antigens, Adjuvant NAcGM3/VSSP Adjuvants, Adjuvant Aluminum Phosphate

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 until death from any cause). Measurement time: weekly during the first 8 weeks) and, later, monthly for two years. Time to radiological progression (Time since patient recruitment until objective tumor progression). Measurement time: 12 and 24 months.

Key secondary outcomes:

Tumor evolution (modified RECIST criteria -mRECIST- and, -RECIL- Response Evaluation Criteria in Cancer of the Liver): Measurement time: 12 and 24 months. Adverse clinical events-AE (occurrence of AE (Yes, No) Description of AE (event name) Intensity of AE (mild, moderate, severe)). Measurement time: at baseline, weekly in during the first 8 immunizations, and thereafter with a monthly frequency throughout the study period. Laboratory (numerical values of hematological and biochemical tests). Measurement time: at baseline and, at weeks 13, 25, 49 and 73. Humoral immune response (determination of anti-VEGF antibody titers; percent inhibition - VEGF binding and its receptor). Measurement time: At weeks 13, 25, 49 and 73. Cellular immune response (ELISPOT for interferon gamma: average number of spots). Measurement time: At week 49. Quality of life (EORTC survey QLQ-C30). Measurement time: at baseline and, months 12 and 24.

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:

70 years

Inclusion criteria:

1) Compliance with diagnostic criteria (established by histological study or non-invasive criteria for the diagnosis of hepatocellular carcinoma in cirrhotic patients or with hepatitis B virus presenting liver lesions greater than 1 cm tumor: Injury greater than or equal to 1 Cm detected by multislice computed tomography or dynamic contrast-enhanced nuclear magnetic resonance, which shows arterial hypervascularization and late portal or portal phase lavage). 2) Age between 18 - 70 years, both inclusive. 3) Patients in stages B or C, according to BCLC (Barcelona Clinic Liver Cancer) staging. a) Patient with a life expectancy ≥ 6 months. b) Functional state according to ECOG ≤ 2. 4) Patient with at least one measurable lesion, according to modified RECIST criteria (mRECIST), and RECIL (Response Evaluation Criteria in Cancer of the Liver). 5) Patient with stabilization or progressive disease at the time of inclusion in the study. 6) Voluntariness of the patient through the signing of informed consent.

Exclusion criteria:

1) Unknown primary tumor. 2) Patients who have received antiangiogenic treatment in the last three months. 3) Have received chemoradiotherapy in the last 4 weeks. 4) Major surgery in the last 28 days. 5) Referred immunosuppressive disease; Ingestion of immunosuppressive / immunomodulatory drugs. 6) Patient with cerebral metastasis. 7) Decompensated chronic diseases (hypertension, diabetes mellitus, chronic renal failure, heart failure, hyperthyroidism, epilepsy). 8) History of autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, etc.) and severe allergic history (urticaria, dermatitis, bronchitis and persistent bronchial asthma). 9) Moderate or severe systemic infections that interfere with patient assessment. 10) History of allergy to any ingredient in the vaccine under study. 11) Patient pregnant or breastfeeding. 12) Obvious mental inability to issue consent and act accordingly with the study.

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:

Uncontrolled

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:

Julio

Middle Name:

Cesar

Last Name:

Hernandez Perera

Specialty:

Doctor of Medical Sciences. Specialist of 2nd degree in Internal Medicine.

Affiliation:

Center for Surgical Medical Research

Postal Address:

Calle 216 y 11b, Reparto Siboney, Playa

City:

Havana

Country:

Cuba

Zip Code:

12100

Telephone:

+537-8581000

Email :

julio.hernandez@infomed.sld.cu [1]

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:

Francisco

Last Name:

Hernandez Bernal

Specialty:

Doctor of Medical Sciences. Specialist of 2nd degree in Hygiene and Epidemiology.

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 entre 158 y 190, Cubanacan, Playa.

City:

Havana

Country:

Cuba

Zip Code:

6162

Telephone:

+537-2085887, +537-2087465

Email :

hernandez.bernal@cigb.edu.cu [2]

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:

RPCEC00000237

Date of Registration in Primary Registry:

16/02/2017

Record Verification Date:

2017/02/16

Next update date:

2018/02/16

Link to the spanish version:

Click here [3]