Intravenous CIGB-128-A in patients with brain tumors (BRATINC 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:

Study of tolerance of the intravenous CIGB-128-A application in recurrent and/or progressive diffuse brain tumors

Secondary indentifying numbers:

IG/AGI/TC/1201

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

Heber Biotec S.A.

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 the Quality of Drugs(CECMED)

Authorization date :

17/11/2012

Reference number:

05.019.12.B

Principal investigator

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

First name:

Agustín Arocha García, MD, Specialist of 2nd grade in neurosurgery

Last name:

Not entered

Affiliation:

Not entered

Postal address:

Not entered

City:

Not entered

País:

Not entered

Zip Code:

Not entered

Email address:

email@not.entered [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, “Saturnino Lora Torres” Hospital, Rafael Domínguez Peña, MD, Specialist of 1st grade in neurosurgery

Research ethics committees:

- “Arnaldo Milián Castro” Hospital, Villa Clara, August 31, 2012. - “Saturnino Lora Torres” Hospital, Santiago de Cuba, August 31, 2012.

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

30/01/2013

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:

Recurrent and/or progressive diffuse brain tumors (benign or malign), at any stage, without other therapeutic options.

Intervention(s):

Study drug: CIGB-128-A (a synergistic combination of alpha and gamma interferons). Route of administration: intravenous (all the groups). Dose: 3.5 MIU (all the groups) It is expected to include until 30 patients whose will be assigned by a dose-scaling manner to 3 groups of treatment (10 patients per group). Group A: 2 times a week: 1 dose (monday and thursday); weekly dose = 7.0 MIU. Group B: 2 times a week: (monday and thursday), monday = 1 dose; thursday = 2 dose; weekly dose = 10.5 MIU. Group C: 2 times a week: 2 dose (monday and thursday); weekly dose = 14 MIU. Treatment duration: 24 weeks (6 months). After that period, CIGB-128-A treatment will be continued according to physician’s decision, until disease progression or death.

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):

Severe adverse events (Yes, No). Measuring time: during the first 6 hours after the first three doses. Afterwards at each administration (questioning) until 6 months of treatment or disease progression or death.

Key secondary outcomes:

Safety variables: Adverse events (AE). Measuring time: during the first 6 hours after the first three doses, afterwards at each administration (questioning) until 6 months of treatment or disease progression or death. - Presence of AE (Yes, No), - Type of AE (name of the AE), - Duration (time between beginning and end of the event), - Intensity of AE (mild, moderate, severe), - Relationship of causality (remote, possible, probable, very probable), - Result of AE (recuperate, improvement, persist or sequels), - Attitude concerning the studied treatment (without changes, dose modification, temporal or definitive treatment discontinuation). Vital signs (body temperature in Celsius degrees, heart rate in beats per minute, blood pressure in mmHg and respiratory rate in breaths per minute). Measuring time: before and at 2h, 4h, and 6h after first 3 injections, and at any moment if symptoms until 6 months of treatment or disease progression or death. Anti-IFN alpha and gamma antibodies [by ELISA Technique: Patients develop antibodies (Yes, No)]. Measuring time: before treatment, month 3 and month 6. Therapeutic effect Radiographic response (CT scans, MRI): Response Assessment in Neuro-Oncology (RANO) criteria. Measuring time: Before treatment, 30 days, 3 months, 6 months, 1 year, and whenever it is possible until the end of treatment. For the most aggressive tumors, evaluations could be more frequent. Progression-free survival at 6 and 12 months (PFS-6; PFS-12. Time from the date of inclusion to the date of disease progression). Measuring time: 6 months, 12 months. Survival at 6 and 12 months (SV-6, SV-12. Time from the date of inclusion to the date of death). Measuring time: 6 months, 12 months. Clinical response: RANO criteria (Complete Response, Partial Response, Stable Disease, Progressive Disease). Measuring time: Before treatment, 30 days, 3 months, 6 months, 1 year, and whenever it is possible until the end of treatment. For the most aggressive tumors, evaluations could be more frequent. Time for clinical response (Time from the date inclusion to the date of clinical response [complete, partial, stable]). Measuring time: 30 days, 3 months, 6 months, 1 year, and whenever it is possible until the end of treatment. For the most aggressive tumors, evaluations could be more frequent. Duration of the clinical response (Time from the the date of clinical response to the date of of recurrence or disease progression). Measuring time: Measuring time: 30 days, 3 months, 6 months, 1 year, and whenever it is possible until the end of treatment. For the most aggressive tumors, evaluations could be more frequent. Time until the therapeutic failure (appearance of serious adverse events at any moment or lesion progression). Measuring time: 3 months of treatment. Functional capacity (Karnofsky scale and/or ECOG). Measuring time: Before treatment, fourth week, 3 and 6 months, then annually if treatment continue. Muscular strength evaluation (Scale of Asia). Measuring time: Before treatment, fourth week, 3 and 6 months, then annually if treatment continue. Steroids use (Yes, No). Measuring time: monthly until the end of treatment. Quality of life (EORTC QLQ-C30 questionnaire). Measuring time: Before treatment, fourth week, 3 and 6 months, then annually if treatment continue. Neuropsychological assessment (Test of Beck). Measuring time: Before treatment, fourth week, 3 and 6 months, then annually if treatment continue.

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:

N/A (No limit)

Inclusion criteria:

1. Age =18 years. 2. Patients with recurrent and/or progressive diffuse brain tumors (benign or malign), with a bad prognostic, without other therapeutic options, at any stage: meningiomas, ependymomas, diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, anaplastic meningioma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma and glioblastoma multiforme, confirmed by histopathological techniques. 3. Recurrent and/or progressive disease diagnosed by imaging (CT scans, MRI) up to 14 days prior inclusion and after the patient has received the conventional treatment that their condition has allowed (Biopsy; Biopsy-RT; Surgery (radio-surgery or another); Surgery-RT; RT; Surgery-RT-Immunotherapy; Surgery-RT-Chemotherapy or another available therapy approved for this kind of patients). 4. Tumor of any size and localization. Taking more than one hemisphere or invasion of basal ganglion, callous body or ventricular system is not prohibited. 5. Karnofsky performance state = 60%. 6. Expectation of life = 8 weeks. 7. Clinical laboratory parameters (up to 7 days previous inclusion): • Hemoglobin = 10 g/L; total leukocytes count = 4 x 109 cells/L; platelets count = 150 x 109/L. • No hepatic alterations at entry demonstrated by AST, ALT or alkaline phosphatase. • Normal renal function: serum creatinine =132 µmol /L. • Normal ionogram. 8. Patients into fertile age should use an effective contraceptive method until three months after the treatment has concluded. 9. Written, informed consent to participate.

Exclusion criteria:

1. Pregnancy, puerperium, or nursing. 2. Hypersensibility to CIGB-128-A or other preparations used in the trial. 3. Medically untreated convulsions. 4. Signs of medullar affectation. 5. Severe coagulation dysfunction. 6. Severe hypertension or ischemic heart disease and/or uncompensated diabetes mellitus proven through clinical examination. 7. Occurrence of congestive heart failure, myocardial stroke, angina or any in-course unstable arrhythmia, that has required medication. 8. Patients treated with immunotherapy over the last month (except Nimotuzumab®) or those that are receiving other type of specific oncological treatment over the last 15 days. 9. Patients that are participating or that recently participated (1 month) in another study, except for phase IV trials with Nimotuzumab®. 10. Sepsis of the Central Nervous System. 11. Severe psychiatric inconvenience or another limitation that impede the patient to give their consent or complicate its evaluation.

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:

Other

Other design:

Dose-scaling

Phase:

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:

Idrian

Last Name:

García-García, MSc

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB)

Postal Address:

Clinical Investigation Department, Ave. 134 /23 and 25, Cubanacán, Playa.

City:

Havana

País:

Cuba

Zip Code:

6332

Telephone:

+53 (7) 2087379; 2087465 ext 108.

Email :

idrian.garcia@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:

Iraldo Idrian

Last Name:

Bello-Rivero, PhD García-García, MSc

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB)

Postal Address:

Clinical Investigation Department, Ave. 134 /23 and 25, Cubanacán, Playa.

City:

Havana

País:

Cuba

Zip Code:

6332

Telephone:

+53 (7) 2087379; 2087465 ext 108.

Email :

iraldo.bello@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:

RPCEC00000140

Date of Registration in Primary Registry:

2013-01-17

Record Verification Date:

2012-12-20 19:00

Link to the spanish version:

Click here [4]