HEBERFERON in renal cell carcinoma

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.

Acronym of Public Title:

ESTHER Study

Scientific title:

Study adaptive, randomized, open, controlled, multicenter Phase I-II, of HEBERFERON use in patients with renal cell carcinoma stage III-IV

Secondary indentifying numbers:

IG/IAG/TR/1401

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:

Raquel

Last name:

Diaz Diaz

Medical Specialty :

First Degree Specialist in Oncology

Affiliation:

“Joaquin Albarran” Hospital

Postal address:

Ave. 26 Boyeros, Puentes Grandes, Plaza de la Revolucion

City:

Havana

País:

Cuba

Zip Code:

10400

Telephone:

+53-78555600

Email address:

gduran@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:

Havana, Carlos J Finlay Hospital, Carlos Alberto Delgado, Medical Doctor.

Havana, Center for Surgical Medical Investigations, Yolanda Cruz Gomez, Master in Sciences.

Havana, National Centre for Minimal Access Surgery, Tania Gonzalez Leon, Medical Doctor.

Havana, Enrique Cabrera Hospital, Juan Carlos Munoz, Medical Doctor.

Matanzas, Jose R. Lopez Tabranes Hospital, Kirenia Camacho, First Degree Specialist in Oncology.

Matanzas, Faustino Perez Hospital, Osmany Luis Leon Ramos, Medical Doctor.

Holguin, Vladimir Ilich Lenin Hospital, Arnel Pupo Ricardo, Medical Doctor.

Sancti Spiritus, Camilo Cienfuegos Hospital, Humberto Penton Valdivia, Medical Doctor.

Villa Clara, Arnaldo Milian Castro Hospital, Rafael Rodriguez Delgado, Medical Doctor.

Santiago de Cuba, Saturnino Lora Hospital, Carlos Ferrer La O, Medical Doctor.

Research ethics committees:

Joaquin Albarran Hospital, November 12, 2015.

Carlos J Finlay Hospital, February 3, 2016.

Center for Surgical Medical Investigations, February 18, 2016.

National Centre for Minimal Access Surgery, October 29, 2015.

Enrique Cabrera Hospital, October 15, 2015.

Jose R. Lopez Tabranes Hospital, January 20, 2016.

Faustino Perez Hospital, February 18, 2016.

Vladimir Ilich Lenin Hospital, November 27, 2015.

Camilo Cienfuegos Hospital, October 22, 2015.

Arnaldo Milian Castro Hospital, July 20, 2015.

Saturnino Lora Hospital, September 22, 2015.

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

03/03/2017

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:

Renal Cell Carcinoma state III and IV after nefrectomy

Health condition(s) code:

Carcinoma, Renal Cell

Adenocarcinoma

Carcinoma

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Urologic Neoplasms

Urogenital Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Female Urogenital Diseases

Intervention(s):

Step of Pharmacokinetic/Pharmacodynamic (PK/PD) Group I (experimental): HeberFERON: Intravenous: 21 MIU, one dose Group II (experimental): HeberFERON: Subcutaneous: 21 MIU, one dose Step of clinical treatment Group A (experimental): HeberFERON: Intravenous: 7.0 MIU, 2 times a week for 4 months. Subcutaneous: 3.5 MIU, 2 times a week for five months. Group B (experimental): HeberFERON: Subcutaneous: 7.0 MIU, 2 times a week for 4 months and 3.5 MIU, 2 times a week for five months. Group C (control): Heberon Alfa2R Subcutaneous: 9.0 MIU 3 times a week for four months; 3.0 MIU 3 times a week for 5 months.

Intervention code:

Interferon-alpha

Interferon-gamma

Interferons

Administration, Intravenous

Injections, Subcutaneous

Intervention keyword:

HeberFERON

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). Measuring time: 12 months.

Key secondary outcomes:

Pharmacokinetics: Serum levels of IFN alfa2b and gamma (result measured by EIA / ELISA). Measurement time: a) For the intravenous route: at baseline (time 0), at minutes 1,5, 15, 30 and 45, and at hours 1, 2, 4, 12, 24, 48, and 72; B) For the subcutaneous route: at baseline (time 0) and in the hours 2, 4, 8, 10, 12, 16, 24, 48, 72. Pharmacodynamics: Quantification of serum levels of Neopterin and 2'-5 'Oligoadenylate synthetase (result measured by EIA / ELISA). Measurement time: a) For the intravenous route: at baseline (time 0) and in the hours 1, 4, 12, 24, 48, 72; B) For the subcutaneous route: at baseline (time 0) and in the hours: 6, 12, 24, 48, 72, 96, 120, 168, 192. Objective response (to be evaluated by RECIST 1.1). Measurement time: at baseline, and at 3, 6 and 12 months of treatment. Disease-free survival (Time from randomization until recurrence of tumor or death from any cause). Measuring time: 6 and 12 months. Progression-free survival (Time from randomization until objective tumor progression or death). Measuring time: 6 and 12 months. Clinical adverse events (AE): - AE occurrence (Yes, No) -Description of AE (name of event) - AE intensity (mild, moderate, severe) - Result (solved completion, solved with sequel, Condition present and unchanged, worsening, death caused by this event) - Causal relationship (unrelated, doubtful, possible, probable, definitive). Measurement time: in each administration. Quality of life (EORTC QLQ-C30 survey: worsened, unchanged, slightly improved, moderately improved, greatly improved). Measurement time: at baseline and in months 3, 6 and 12.

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:

None

Inclusion criteria:

1. Characteristics of the disease: 1.1. Histological or cytological diagnosis of stage III or IV renal cell carcinoma after nephrectomy. 1.2. Measurable or non-measurable disease that includes any of the following: 1.2.1. Measurable lesion in a dimension ≥ 20 mm by conventional methods (physical examination, X-ray) or 10 mm by CT or MRI. The following are considered non-measurable diseases: -Lessions small. -Lion in bone -Leptomeningeal disease -Ascitis - Pleural / pericardial fusion - Lymphangitis cutis / pulmonis. Abdominal mass not confirmed and followed by imaging techniques. - Cystic lesions. - Irradiated lesions, while progression is not documented after radiotherapy. -1.3. Availability of non-stained paraffin blocks or sheets. -1.4. Imaging evaluation that defines the absence or presence of metastases (CT, MRI or other available). 2. Characteristics of patients: 2.1. Age ≥18 years, any gender and race. 2.2. ECOG ≤2 / KPS≥70. 2.3. Hematopoietic parameters 2.3.1. Granulocyte count ≥ 1.5 x 109 / L 2.3.2. Platelet count ≥ 100 x 109 / L 2.3.3. No clinical history of significant bleeding. 2.4. Hepatic parameters 2.4.1. ASAT / ALAT ≤ 2.5 upper limit of normal (LNS) 2.4.2. Alkaline phosphatase 2.5 ≤ LNS 2.4.3. Bilirubin ≤ 1.5 LNS 2.5. Renal parameters 2.5.1. Creatinine ≤ 1.5 LNS 2.5.2. Without proteinuria> 1+ 2.5.3. Proteinuria ≥ 2+ allowed with protein <2 g / 24-hour in the urine 2.6. Clinical condition and parameters (hematopoietic, hepatic, renal and cardiac) in the ranges established previously after the FC / FD study 3. Previous or concurrent therapies. 4. Other types of prior or concurrent antitumor treatments are not prohibited or to compensate for non-decompensated chronic noncompensated chemical, radiation, biological, endocrine, or concomitant diseases. 5. Surgery. At least 4 weeks after surgery and with regrowth criteria. 6. Other 6.1. Negative pregnancy test. 6.2. Patients of childbearing potential should use an effective contraceptive method. 6.3. Express written willingness of the patient.

Exclusion criteria:

1. Cardiovascular parameters. 1.1. Myocardial infarction in the last 6 months prior to the administration of the product. 1.2. Severe or unstable angina 1.3. Implant of coronary or peripheral bypass. 1.4. Symptomatic congestive heart failure. 1.5. Stroke or transient ischemic attack. 1.6. Pulmonary embolism. 1.7. Presence of ventricular arrhythmias ≥ grade 2 1.8. Absence of HPA which cannot be controlled by drugs. 2. Pregnancy, postpartum and breastfeeding. 3. Active infection requiring any specific treatment. 4. ALT or AST> 5 times the normal reference range. 5. Decompensated chronic diseases (hypertension, diabetes mellitus, chronic renal failure, heart failure, ischemic heart disease or other symptomatic cardiovascular disease, epilepsy, severe mental depression). 6. Antecedents of severe allergic urticarial, atopic dermatitis, bronchitis or persistent bronchial asthma or any ingredients of the formulations under study. 7. Obvious mental disability or other limitation that prevents the patient to sign the consent or difficult study evaluations.

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:

Active

Study design:

Parallel

Phase:

1-2

Target sample size:

270

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:

Iraldo

Last Name:

Bello Rivero

Specialty:

Doctor of Biological Sciences

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

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

City:

Havana

País:

Cuba

Zip Code:

10600

Telephone:

(53-7)-2085887, (53-7)-2087465

Email :

iraldo.bello@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

Last Name:

Bello Rivero

Specialty:

Doctor of Biological Sciences

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

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

City:

Havana

País:

Cuba

Zip Code:

10600

Telephone:

(53-7)-2085887, (53-7)-2087465

Email :

iraldo.bello@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:

RPCEC00000229

Date of Registration in Primary Registry:

05/01/2017

Record Verification Date:

2017/01/05

Next update date:

2018/01/05

Link to the spanish version:

Click here [3]