HEBERFERON in renal cell carcinoma

• Register: RPCEC
• Last refreshed on: 29 April 2024
• Main ID: RPCEC00000229
• Date of registration: 05/01/2017
• Prospective Registration: Yes
• Primary sponsor: Center for Genetic Engineering and Biotechnology (CIGB), in Havana
• Public title: HEBERFERON in renal cell carcinoma
• Scientific title: Study adaptive, randomized, open, controlled, multicenter Phase I-II, of HEBERFERON use in patients with renal cell carcinoma stage III-IV
• Date of first enrolment: 03/03/2017
• Target sample size: 270
• Recruitment status: Pending
• URL: https://rpcec.sld.cu/en/trials/RPCEC00000229-En
• Study type: Interventional
• Study design: Allocation: Randomized controlled trial. Masking: Open. Control group: Active. Assignment: Parallel. Purpose: Treatment
• Phase: 1-2

Countries of recruitment

Cuba

Contacts

• Name: Iraldo Bello Rivero
• Affiliation: Center for Genetic Engineering and Biotechnology (CIGB).

• Name: Iraldo Bello Rivero
• Affiliation: Center for Genetic Engineering and Biotechnology (CIGB).

Key inclusion & exclusion criteria

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.

Age minimum: 18 years
Age maximum: None
Gender: Male/Female

Health Condition(s) or Problem(s) studied

Urologic Diseases

Renal Cell Carcinoma state III and IV after nefrectomy

Urogenital Neoplasms

Urologic Neoplasms

Adenocarcinoma

Female Urogenital Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Diseases

Kidney Neoplasms

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

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.

Interferon-gamma

Interferons

Injections, Subcutaneous

Administration, Intravenous

HeberFERON

Interferon-alpha

Primary Outcome(s)

Overall survival (Time from randomization until death from any cause). Measuring time: 12 months.

Secondary Outcome(s)

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.

Secondary ID(s)

IG/IAG/TR/1401

Source(s) of Monetary Support

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

Secondary Sponsor(s)

Not applicable