CENTAURO-4 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:

Clinical trial of CIGB-247 in patients with ovarian epithelial cancer, fallopian tubes and/or peritoneum in advanced stages inoperable or after suboptimal surgery.

Secondary indentifying numbers:

IG/CIGB-247I/CO/1604

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

Center for Genetic Engineering and Biotechnology (CIGB), Havana. Ministry of Public Health, CUBA.

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:

Raiza

Last name:

Ruiz Lorente

Medical Specialty :

2nd Degree Specialist in Oncology

Affiliation:

"Ramon Gonzalez Coro" Gynecobstetric Hospital

Postal address:

21 No. 854 between 4 and 6, Vedado

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

+53-78339302

Email address:

raizaruiz@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:

Pinar del Rio, III Congreso Hospital, Yamirka Sanchez Azcuy, MD. 2nd Degree Specialist in Oncology.

Havana, Center for Medical-Surgical Research, Katty-Hind Selman-Housein Bernal, MD. 2nd Degree Specialist in Internal Medicine.

Matanzas, “Jose Ramon Lopez Tabranes” Hospital, Kirenia Camacho Sosa, MD. 2nd Degree Specialist in Oncology.

Villa Clara, “Celestino Hernandez" Hospital, Saylin Alfonso Aleman, MD. 2nd Degree Specialist in Oncology.

Cienfuegos, “Gustavo Aldereguia" Hospital, Doris Gonzalez Diaz, MD. 2nd Degree Specialist in Gynecology and Obstetrics.

Sancti Spiritus, “Camilo Cienfuegos" Hospital, Yanelis Leon Duran, MD. 2nd Degree Specialist in Oncology.

Ciego de Avila, “Antonio Luaces" Hospital, Gissel Guevara Artiles, MD. 2nd Degree Specialist in Oncology.

Camagüey, “Marie Curie” Hospital, Gustavo Crespo Campo, MD. 2nd Degree Specialist in Gynecology and Obstetrics.

Las Tunas, “Ernesto Che Guevara" Hospital, Eliecer Santiesban Gonzalez, MD. 2nd Degree Specialist in Oncology.

Granma, “Carlos Manuel de Cespedes” Hospital, Maria del Carmen Olivera Rodriguez, MD. 2nd Degree Specialist in Oncology.

Granma, “Celia Sanchez" Hospital, Luis Alberto Villega Ramos, MD. 2nd Degree Specialist in Oncology.

Santiago de Cuba, “Juan Bruno Zayas" Hospital, Yolaida Castellanos Ramirez, MD. 2nd Degree Specialist in Oncology.

Santiago de Cuba, “Conrado Benitez" Hospital, Cesar Gonzalez Alonso, MD. 2nd Degree Specialist in Oncology.

Guantanamo, "Agostinho Neto" Hospital, Lidia Esther Lorié Sierra, MD. 2nd Degree Specialist in Oncology.

Research ethics committees:

III Congreso Hospital, May 18, 2016.

"Ramón Gonzalez Coro" Gynecobstetric Hospital, June 06, 2016.

Center for Medical-Surgical Research, June 23, 2016.

“José Ramon Lopez Tabranes” Hospital, May 18, 2016.

“Celestino Hernandez" Hospital, May 10, 2016.

“Gustavo Aldereguia" Hospital, May 12, 2016.

“Camilo Cienfuegos" Hospital, May 19, 2016.

“Antonio Luaces" Hospital, May 13, 2016.

“Marie Curie” Hospital, June 28, 2016.

“Ernesto Che Guevara" Hospital, May 30, 2016.

“Carlos Manuel de Cespedes” Hospital, May 11, 2016.

“Celia Sanchez" Hospital, June 15, 2016.

“Juan Bruno Zayas" Hospital, May 26, 2016.

“Conrado Benitez" Hospital, May 13, 2016.

"Agostinho Neto" Hospital, May 20, 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:

02/05/2017

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:

Cancer of ovary, fallopian tubes and / or peritoneum.

Health condition(s) code:

Carcinoma

Ovarian Neoplasms

Fallopian Tube Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Peritoneal Neoplasms

Abdominal Neoplasms

Ovarian Diseases

Genital Diseases, Female

Female Urogenital Diseases

Fallopian Tube Diseases

Adnexal Diseases

Peritoneal Diseases

Intervention(s):

Group I (experimental): Chemotherapy (Carboplatin and paclitaxel, 6 cycles every 21 days) b y intravenous route + Antigen p64K-hVEGFKDR- (800 μg) + synthetic NAcGM3s/VSSP (200 µg) applied subcutaneously in the deltoid region (weekly schedule for 8 weeks , followed by monthly boosters every 28 days, for 18 months). Group II (experimental): Chemotherapy (Carboplatin and paclitaxel, 6 cycles every 21 days) by intravenous route + Antigen p64K-hVEGFKDR- (800 μg) + Aluminum phosphate (0.7 mg AL3 +) applied subcutaneously in the deltoid region (weekly schedule for 8 weeks , followed by monthly boosters every 28 days, for 18 months).

Intervention code:

Carboplatin

Paclitaxel

Drug Therapy, Combination

Antigens

G(M3) Ganglioside

Gangliosides

Proteolipids

N-Acetylneuraminic Acid

Adjuvants, Immunologic

Vaccines

Administration, Intravenous

Injections, Subcutaneous

Intervention keyword:

CIGB-247, NAcGM3s/VSSP, Aluminum Phosphate, p64K-hVEGFKDR Antigens

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):

Progression-free survival (Time from inclusion in the study to the onset of progressive disease or death). Measurement time: months 1, 6, 12, 18 and 24 after the start of treatment.

Key secondary outcomes:

1. Global Survival (Time from randomization of the patient in the study to the death or date of latest news). Measurement time: months 1, 6, 12, 18 and 24 after the start of treatment 2. Objective response: To be evaluated according to the criteria of RECIST (Response evaluation criteria in solid tumors). Patients will be classified as: complete response, partial response, stable disease or progressive disease. Measurement time: every 3 months until 24 months. 3. Humoral immune response (determination of anti-VEGF antibody titres; percent inhibition - VEGF binding and its receptor) and cellular (ELISPOT for interferon gamma: average number of spots). Time of measurement: at weeks 13, 25, 49 and 73 (humoral response); At week 49 (cell response). 4. Quality of life (through validated EORTC survey for this disease QLQ-C30 and QLQ-LC13). Measurement time: every 3 months until 24 months. 5. Adverse clinical events (occurrence of AD (Yes, No) Description of AD (event name) Intensity of AD (mild, moderate, severe) Measurement time: at baseline, weekly in during the first 8 immunizations, and thereafter with a monthly frequency until 24 months. 6. Laboratory (numerical values of hematological and biochemical tests). Measurement time: initial and in Measurement time: at weeks 13, 25, 49 and 73.

Selection criterias

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

Gender:

Female

Minimum age:

18 years

Maximum age:

75 years

Inclusion criteria:

1) Patients with confirmed cytological / histological criteria for ovarian epithelial carcinoma, fallopian tubes and / or peritoneum. 2) Age between 18 and 75 years, both inclusive. 3) Patients with Performance status 0-1 4) Patients with normal hepatic, renal and hematologic functions defined by: - Hemoglobin ≥ 90 g / L (patients with lower levels of Hb can be transfused and reevaluate 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 normal upper limit. - TGP and TGO: up to ≤ 1.5 times the upper limit for the normal value of the institution, or <5 times the upper limit for the normal value of the institution, if liver metastases are known. - Alkaline phosphatase ≥ 2.5 times the normal upper limit. - Creatinine: Within normal limits for each institution or creatinine clearance> 50 mL / min / 1.73 m2 for patients with creatinine levels above the normal value of the institution For patients with bone metastases, the inclusion of patients with alkaline phosphatase <5 x ULN will be permitted, provided that ALT and AST <1.5 x ULN, assuming in these cases that the elevation of alkaline phosphatase is due exclusively to metastases Bony 5) Voluntary patient by signing the informed consent.

Exclusion criteria:

1) Patients included in another clinical trial and who have received any biological therapy under investigation, including active or passive immunotherapy in the last 6 months. 2) Referred immunosuppressive disease; Ingestion of immunosuppressive / immunomodulatory drugs. 3) Patient with tumor or brain metastasis. 4) Decompensated chronic diseases (hypertension, diabetes mellitus, chronic renal failure, heart failure, hyperthyroidism, epilepsy). 5) Moderate or severe systemic infections that interfere with patient assessment. 6) History of allergy to any ingredient in the vaccine under study. 7) Patients who are pregnant or breastfeeding: (Patients of childbearing age should have a negative pregnancy test before starting treatment and follow a contraceptive method approved during the study and up to 3 months later) 8) Obvious mental incapacity to issue consent and act accordingly with the study. 9) Patients with no feasibility of attending scheduled follow-up.

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:

2-3

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:

Idania

Last Name:

Baladron Castrillo

Specialty:

2nd Degree Specialist in Gynecology and Obstetrics.

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 :

idania.baladron@cigb.edu.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:

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:

Habana

Country:

Cuba

Zip Code:

6162

Telephone:

+537 2716022

Email :

hernandez.bernal@cigb.edu.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:

RPCEC00000246

Date of Registration in Primary Registry:

30/04/2017

Record Verification Date:

2017/04/30

Next update date:

2018/04/30

Link to the spanish version:

Click here [4]