Phase I/II trial with the mutein no alfa of IL-2

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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:

Dose escalation study and expansion cohorts with the IL-2 non-alpha Mutein in patients with solid tumors in advanced stages. Phase I/II

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), Cuba Ministry of Public Health (MINSAP), 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:

Marta

Last name:

Osorio Rodriguez

Medical Specialty :

Second Degree Specialist in Oncology

Affiliation:

National Institute for Oncology and Radiobiology (INOR)

Postal address:

29st. & F ave. Vedado, Plaza de la Revolucion

City:

Havana

País:

Cuba

Zip Code:

10400

Telephone:

+53-78369209

Email address:

mcosorio@infomed.sld.cu

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:

National Center for Oncology and Radiobiology, September 2nd, 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:

01/03/2017

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:

Solid tumors

Health condition(s) code:

Neoplasms

Health condition keyword:

Solid tumors

Intervention(s):

Stage I Group 1, dose level 1 (Experimental): 3000 U/kg of Il-2 not alpha mutein intravenously in not less than 15 minutes, a dose every 8 hours up to 14 doses (cycle 1). The patient will rest for 9 days and the same number of doses will be administered in the second cycle. Group 2, dose level 2 (Experimental): 6000U/kg of Il-2 not alpha mutein intravenously in not less than 15 minutes, a dose every 8 hours up to 14 doses (cycle 1). The patient will rest for 9 days and the same number of doses will be administered in the second cycle. Group 3, dose level 3 (Experimental): 12000U/kg of Il-2 not alpha mutein intravenously in not less than 15 minutes, a dose every 8 hours up to 14 doses (cycle 1). The patient will rest for 9 days and the same number of doses will be administered in the second cycle. Stage II The selected dose will use in 3 cohort of patients according to tumor type.

Intervention code:

Interleukin-2

Interleukins

Cytokines

Administration, Intravenous

Intervention keyword:

mutein no alfa of IL-2

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):

Maximum Tolerated Dose-MTD (Level where included 6 subjects). Measuring time: at the end of stage I. The MTD will use in the stage II (expansion to 3 cohort of patients according to tumor type) Serious adverse events with causality relationship proved (definitive, very likely, likely) with product administration. Measuring time: every 1 or 4 hours if needed during product administration.

Key secondary outcomes:

1. Objective Response Rate (Complete response, Partial response according to RECIST 1.1). Measuring time: at baseline, 4 weeks after last dose of second cycle and, Months 6, 9 and 12. 2. Overall Survival (Time from randomization until death from any cause or until last news). Measuring time: 12 months. 3. Progression-Free Survival-PFS (time from randomization until objective tumor progression or death).Measuring time: 12 months. 4. Response duration (time from patient’s response until objective tumor progression or death). Measuring time: up to 12 months in patients with objective response. Immunological response 1. Expansion of effector T lymphocyte populations. Measurement time: at baseline, 24 hours after cycles 1 and 2. 2. Natural killer cells (NK). Measurement time: at baseline, 24 hours after cycles 1 and 2. 3. Regulatory T lymphocytes (Treg). Measurement time: at baseline, 24 hours after cycles 1 and 2. 4. Memory subpopulations. Measurement time: at baseline, 24 hours after cycles 1 and 2. 5. Activation Parameters. Measurement time: at baseline, 24 hours after cycles 1 and 2. Pharmacokinetic parameters. In stage II: 1. Bioavailability-F (estimated value using Monolix system, with SAEM algorithm combined with Monte Carlo code). Measuring time: after first dose of cycle 1 and, after last dose of cycles 1 and 2 with a design of few data in block of 4 patients where every patient has 14 extractions. 2. Volume of distribution -V (estimated value using Monolix system, with SAEM algorithm combined with Monte Carlo code). Measuring time: after first dose of cycle 1 and, after last dose of cycles 1 and 2 with a design of few data in block of 4 patients where every patient has 14 extractions. 3. Elimination rate constant -k (estimated value using Monolix system, with SAEM algorithm combined with Monte Carlo code). Measuring time: after first dose of cycle 1 and, after last dose of cycles 1 and 2 with a design of few data in block of 4 patients where every patient has 14 extractions. 4. Maximum Plasma Level -Cmax (estimated value using Monolix system, with SAEM algorithm combined with Monte Carlo code). Measuring time: after first dose of cycle 1 and, after last dose of cycles 1 and 2 with a design of few data in block of 4 patients where every patient has 14 extractions. 5. Elimination half-life -T 1/2 (estimated value using Monolix system, with SAEM algorithm combined with Monte Carlo code). Measuring time: after first dose of cycle 1 and, after last dose of cycles 1 and 2 with a design of few data in block of 4 patients where every patient has 14 extractions. 6. Plasma Clearance - Cl (estimated value using Monolix system, with SAEM algorithm combined with Monte Carlo code). Measuring time: after first dose of cycle 1 and, after last dose of cycles 1 and 2 with a design of few data in block of 4 patients where every patient has 14 extractions. Safety 1. Adverse Events-AE (Occurrence of any AE [Yes, No], description [name of AE], duration [ time from begin date until end date of AE], intensity [Mild, Moderate, Severe, Life-threatening or disabling AE, Death related to AE], gravity [Serious o Not serious, No proceed (NP)], result [recovered, better, persist, sequelae], attitude [without change, dose modification, temporary interruption, definitive interruption], causality relationship [1.Definitive, 2.Very likely, 3.Likely, 4.Possible, 5.No related, 6.Unknown], treatment indicated for AE [medicines indicated for AE], product batch [batch number]). Measuring time: every 1 or 4 hours if needed during the product administration, 4 weeks after last administration and, months 6, 9 and 12. 2. Laboratory test-hematology (values of hemoglobin, hematocrit, leukogram with differential and platelets). Measuring time: at baseline, 4 weeks after last dose and, months 6, 9 and 12. 3. Laboratory test- biochemistry (values of alkaline phosphatase, AST [GOT], ALT [GPT], creatinine, complete and direct bilirubin). Measuring time: at baseline, 4 weeks after last dose and, months 6, 9 and 12. 4. Vitals signs (Blood pressure [mmg], Cardiac frequency [min], temperature [0C]). Measuring time: every 1 or 4 hours if needed during product administration and, months 6, 9 and 12. 5. Cardiac function (Echocardiogram result). Measuring time: at baseline, 4 weeks after finished last cycle. 8. Physical exam (every system will be evaluated in normal, abnormal [according to findings], not done [if no examined]). Measuring time: before product administration and y 1 hour later, months6, 9 and 12. 6. Antibody against Mutein (Present or not). Measuring time: at baseline, 24 hours after cycles 1 and 2.

Selection criterias

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

Gender:

Male

Minimum age:

18 years

Maximum age:

None

Inclusion criteria:

1. Patients who meet the diagnostic criteria. 2. Patients who give their written informed consent to participate. 3. Patients of either sex aged over 18 years. 4. Patients generally ≤ 2 state (as ECOG). 5. Patients with a life expectancy of at least 6 months. 6. Patients having functioning of organs and bone marrow under pre-defined parameters.

Exclusion criteria:

1. Patients of childbearing age who are not using an appropriate method of contraception prior to inclusion in the study (intrauterine devices, hormonal contraceptives, barrier methods or tubal ligation). If male (vasectomy, condom use). 2. Pregnant or lactating patients. 3. Patients with acute allergic conditions or history of severe allergic reactions. 4. Patients with acute decompensated chronic lung disease or that may interfere with the monitoring of the underlying disease. 5. Patients with previous history of demyelinating inflammatory or central nervous system disease (CNS) or peripheral (PNS). 6. Patients suffering from uncontrolled intercurrent illness including, but not limited to: active infections, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, diabetes mellitus and psychiatric diseases involving the incompetence of the subject. 7. Patients with brain metastases. 8. Patients who are receiving other investigational product. 9. Patients with known hypersensitivity to any component of the formulation. 10. Patients with known HIV positive serology, hepatitis B or C.

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:

Single group

Phase:

1-2

Target sample size:

66

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:

Ivis

Last Name:

Mendoza Hernandez

Specialty:

Bachelor in Pharmaceutical Sciences and Master in Pharmacology

Affiliation:

National Coordinating Center for Clinical Trials (CENCEC)

Postal Address:

5ta A st. between 60 & 62. Miramar. Playa

City:

Havana

País:

Cuba

Zip Code:

11300

Telephone:

+537-2164227

Email :

ivis@cencec.sld.cu

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:

Pedro

Middle Name:

Camilo

Last Name:

Rodriguez Rodriguez

Specialty:

Medical doctor, Second Degree Specialist in Pharmacology

Affiliation:

Center of Molecular Immunology

Postal Address:

216 st. & 15 ave. Atabey, Playa

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

+53-72717933

Email :

camilo@cim.sld.cu

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:

RPCEC00000234

Date of Registration in Primary Registry:

03/02/2017

Record Verification Date:

2017/02/03

Next update date:

2018/02/03

Link to the spanish version:

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Phase I/II trial with the mutein no alfa of IL-2

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