Biodistribution of CIGB-300 in cervical cancer (CERVIFARM-300-II 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:

Biodistribution and pharmacokinetics, safety and therapeutic effect of the CIGB-300 application in the epidermoid carcinoma of the uterine neck stage IB2-II

Secondary indentifying numbers:

IG/CIGB300I/CC/0902

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

HeberBiotec S.A. Chemo Group

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 :

07/07/2009

Reference number:

05.009.09.B

Principal investigator

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

First name:

Miguel Román Sarduy Nápoles, PhD, 2nd degree specialist in Gynecology and Obstetrics.

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:

- Havana, Center of Clinical Investigations, Caridad Alina Casacó Santana, MD, 2nd degree specialist in radiology - Havana, Gineco-Obstetrician Hospital “Clodomira Acosta Ferrales”, Margarita Solares Asteasuainzarra, MD, 2nd degree specialist in Gynecology and Obstetrics.

Research ethics committees:

- Medical – Surgical Research Center, March 13, 2009. - Center of Clinical Investigations, December 7, 2009. - Gineco-Obstetrician Hospital “Clodomira Acosta Ferrales”, April 1st, 2009.

Recruitment status

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

Recruitment status:

Complete

Date of first enrollment:

18/01/2010

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:

Cervical epidermoid carcinoma, stage IB2-II.

Intervention(s):

Study group (CIGB-300, 35 mg): Doses of 35 mg resuspended in 1 ml of water for injection, applied by intratumor route in 3 cycles of daily applications for 3 days in the weeks 1, 3 and 5, respectively. In each cycle, the product will be administered as unique treatment (simple agent), and after the last cycle (week 5) the conventional chemo-radiotherapy (CRT) treatment will begin. Conventional chemo-radiotherapy consists in cisplatin 40 mg/m2, once per week, during 6 weeks, concomitant to 5040 cGy of external beam radiotherapy given in 28 fractions. This will be followed by 2600 cGy of intracavitary radiotherapy given in 4 high dose fractions (650 cGy/day) over 2 weeks. Study group (CIGB-300, 70 mg): Doses of 70 mg resuspended in 1 ml of water for injection, applied by intratumor route in 3 cycles of daily applications for 3 days in the weeks 1, 3 and 5, respectively. In each cycle, the product will be administered as unique treatment (simple agent), and after the last cycle (week 5) the conventional CRT treatment will begin. Conventional chemo-radiotherapy consists in cisplatin 40 mg/m2, once per week, during 6 weeks, concomitant to 5040 cGy of external beam radiotherapy given in 28 fractions. This will be followed by 2600 cGy of intracavitary radiotherapy given in 4 high dose fractions (650 cGy/day) over 2 weeks. These two dose levels were well-tolerable in the previous study CERVIFARM-300, where 70 mg was the maximum tolerable dose.

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):

Biodistribution and Pharmacokinetics Biodistribution (Body gammagraphy. Distribution of the radiolabeled peptide in tumor and main source organs). Measuring time: 10 min, 1h, 2h, 4h, 8h, 12h y 24h after the first administration. Pharmacokinetic studies in serum, whole blood and urine (measurement of activity, and quantification of CIGB-300 serum by ELISA and HPLC). Measuring time: Immediately, 5 min, 15 min, 30 min, 1h, 2h, 4h, 8h, 12h y 24h after the first dose. The urine will be collected at intervals during this sampling period to determine the excreted magnitude and renal clearance.

Key secondary outcomes:

Safety variables: Presence of severe adverse events (Yes, No). Measuring time: at each administration. Presence of clinical Adverse Events (AE). Measuring time: at each administration. - Appearance of AE (Yes, No) - Type of AE (name of the AE) - Duration of AE (time from appearance to end of the event) - Intensity of AE (mild, moderate, severe) - Relation 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 each dose, at 30min, 1h, 1h, 2h, 3h, 4h and 12h after each dose. Laboratory tests hemoglobin, white blood cells counts, globular sedimentation rate, coagulation parameters, glucemy, transaminases, bilirubin, alkaline phosphatase, urea, creatinine). Measuring time: Before and 24 hours after each CIGB-300 cycle. Afterwards weekly during chemo-radiotherapy and each three months during a one-year follow-up. Histamine plasmatic levels (ELISA techniques). Measuring time: At baseline, 5min, 15min,30min and 60min after the first dose. Therapeutic response: Clinical colposcopic evaluation (Size of the tumoral lesion in diameters and area of the tumor surface captured by digital picture and measured using MADIP software). Measuring time: Before and 24 hours after each cycle and whenever it is required by safety requirements. Biweekly during CRT and quarterly until complete 1 year after CRT. Imagenological evaluation (Tumor size using abdominal and transvaginal ultrasonography, CT scans, MRI, according to the evaluation criteria for solid tumors-RECIST). Measuring time: Before CIGB-300 treatment. After the last CIGB-300 cycle (week 5). After the whole treatment quarterly until complete 1 year. Biological response: Expression of B23/nucleophosmin in tumors (Immunohistochemistry análisis) in paraffin-embedded tumor biopsies will be carried out. Measuring time: before CIGB-300 treatment and 24 hours after the third (last) cycle. Anti-B23 (nucleophosmin) antibodies (ELISA techniques). Measuring time: At baseline, 24h after 3rd cycle and 3 months after chemo-radiotherapy.

Selection criterias

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

Gender:

Female

Minimum age:

18 years

Maximum age:

75 years

Inclusion criteria:

1. Clinical, imagenological and histological diagnosis of stage IB-II epidermoid cervical cancer. 2. Age between 18-75 years, both included. 3. Written informed consent by the patient. 4. Clinical laboratory parameters within normal limits. 5. General health index from 0 to 2, according to WHO classification. 6. Life expectation of more than 1 year.

Exclusion criteria:

1. To have received surgical, ablative or immunomodulatory treatment during the 30 days before inclusion. 2. Body Mass Index lower than 19 or greater than 30. 3. Pregnancy or nursing. 4. Other decompensate chronic disease (arterial hypertension, diabetes mellitus, chronic renal disease, cardiac insufficiency,hyperthyroidism, malignant neoplasia, epilepsy, severe mental depression). 5. Previous diagnosis of dysfunction of coagulation and other decompensate chronic hematopahies (hemophilia, leukemia, among other). 6. Clinical laboratory values outside normal ranges before the treatment. 7. Referred Immunosuppressor disease and current ingestion of immunosuppressor / immunomodulating drugs (including steroids) 30 days previous the study. 8. Autoimmune disorders (Systemic Lupus Erythematosus, Rheumatoid Arthritis, Multiple Sclerosis, Type 1 Diabetes Mellitus, etc.) and severe allergic antecedents such as Urticaria, Dermatitis, Bronchitis and persistent Bronchial Asthma. 9. Febrile illness (temperature >37.8°C) at time or 24 hours before administration of the product or acute infectious disease suspected by clinical examination. 10. Diseases that compromise the state of the patient's conscience or their possibility to give informed consent or collaborate in the trial. 11. Tumoral extensive necrosis that prevent the application of the product as indicate the protocol. 12. To be included in another clinical trial or to have been included in a previous trial the last 8 weeks prior to inclusion.

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:

Double Blind

Control group:

Uncontrolled

Study design:

Parallel

Phase:

Target sample size:

12-16

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 between 23 and 25, Cubanacán, Playa.

City:

Havana

País:

Cuba

Zip Code:

6332

Telephone:

+53 (7) 2087377; 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:

Idrian

Last Name:

García-García, MSc

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB)

Postal Address:

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

City:

Havana

País:

Cuba

Zip Code:

6332

Telephone:

+53 (7) 2087377; 2087379; 2087465 ext 108.

Email :

idrian.garcia@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:

RPCEC00000142

Date of Registration in Primary Registry:

2013-01-18

Record Verification Date:

2013-01-08 19:00

Link to the spanish version:

Click here [3]