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

• Register: RPCEC
• Last refreshed on: 27 May 2013
• Main ID: RPCEC00000140
• Date of registration: 17/01/2013
• Primary sponsor: Center for Genetic Engineering and Biotechnology (CIGB)
• Public title: Intravenous CIGB-128-A in patients with brain tumors (BRATINC Study)
• Scientific title: Study of tolerance of the intravenous CIGB-128-A application in recurrent and/or progressive diffuse brain tumors
• Date of first enrolment: 30/01/2013
• Target sample size: 30
• Recruitment status: Pending
• URL: http://registroclinico.sld.cu/trials/RPCEC00000140-En
• Study type: Interventional
• Study design: Randomization: Nonrandomized Trial Blinding: Open. Placebo: Uncontrolled Assignment: Other Purpose: Treatment Other design features: Dose-scaling

Countries of recruitment

Cuba

Contacts

• Name: Idrian García-García, MSc
• Affiliation: Center for Genetic Engineering and Biotechnology (CIGB)

• Name: Iraldo Idrian Bello-Rivero, PhD García-García, MSc
• Affiliation: Center for Genetic Engineering and Biotechnology (CIGB)

Key inclusion & exclusion criteria

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.

Age minimum: 18 years
Age maximum: N/A (No limit)
Gender: Both

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.

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.

Secondary Outcome(s)

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.

Secondary ID(s)

IG/AGI/TC/1201

Source(s) of Monetary Support

Heber Biotec S.A.

Secondary Sponsor(s)

Ministry of Public Health, Cuba.