Diphenhydramine previous to CIGB-300 in cervical carcinoma (CERVISEG-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:

Safety of the CIGB-300 application associated to diphenhydramine pre-medication in the epidermoid carcinoma of the uterine neck stage Ib2-II. Phase I study.

Secondary indentifying numbers:

IG/CIGB-300 I/CC/0901

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 :

29/06/2009

Reference number:

05.036.09.B

Principal investigator

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

First name:

- Regla Fang Mederos, MD, 1st degree specialist in Gynecology and Obstetrics. - Doris González Díaz, MD, 1st degree specialist in Gynecology and Obstetrics.

Last name:

Not entered

Affiliation:

Not entered

Postal address:

Not entered

City:

Not entered

Country:

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

Research ethics committees:

- Hospital “Gustavo Aldereguía Lima”, Cienfuegos, February 24, 2009. - Oncology Hospital “Celestino Hernández Robau”, Villa Clara. April 21, 2009. - Hospital “Carlos Manuel de Céspedes”, Bayamo, November 17, 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:

27/01/2010

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, 70 mg): CIGB-300 + CRT CIGB-300: Doses of 70 mg resuspended in 1 ml of water for injection, applied by intratumor route once per day, during 5 days, in one injection site, in the center of lesion, during 10-15 min. Previous pre-medication with diphenhydramine was applied 30 minutes previous CIGB-300 administration. Chemo-radiotherapy (CRT): 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 (650cGy/day) over 2 weeks. The CRT will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology. Study group (CIGB-300, 105 mg): CIGB-300 + CRT CIGB-300: Doses of 105 mg resuspended in 1 ml of water for injection, applied by intratumor route once per day, during 5 days, in one injection site, in the center of lesion, during 10-15 min. Previous pre-medication with diphenhydramine was applied 30 minutes previous CIGB-300 administration. Chemo-radiotherapy (CRT): 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 (650cGy/day) over 2 weeks. The CRT will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology. Study group (CIGB-300, 175 mg): CIGB-300 + CRT CIGB-300: Doses of 175 mg resuspended in 1 ml of water for injection, applied by intratumor route once per day, during 5 days, in one injection site, in the center of lesion, during 10-15 min. Previous pre-medication with diphenhydramine was applied 30 minutes previous CIGB-300 administration. Chemo-radiotherapy (CRT): 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 (650cGy/day) over 2 weeks. The CRT will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology.

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):

Presence of severe adverse events (Yes, No). Measuring time: until 24 hours after each CIGB-300 dose.

Key secondary outcomes:

Safety variables: Clinical adverse events (AE). Measuring time: until 24 hours after each CIGB-300 administration. Then, patients will be followed for safety during chemo-radiotherapy and each three months until one year after this. - Presence of AE (Yes, No), - Type of AE (Name of the AE), - Duration of the AE (time from appearance to end of the event), - Intensity of the AE (mild, moderate, severe), - Relation of causality of the AE (remote, possible, probable, very probable), - Result of the 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 mm Hg and respiratory rate in breaths per minute). Measuring time: before CIGB-300, at 30 minutes, 1h, 1h, 2h, 3h, 4h, 12h and 24h after injection. Laboratory tests (hemoglobin (g/L), hematocrit (L/L), leucocyte counts (x109/L), platelet count (x109/L), globular sedimentation rate (mm/h), glucemy (mmol/L), serum creatinine (?mol/L), AST (IU/L), ALT (IU/L). Measuring time: Before and 21 days after CIGB-300 treatment. Later weekly during chemo-radiotherapy and each three months during a one-year follow-up. Therapeutic response: Clinical-colposcopical evaluation: Size of the tumoral lesion (diameters and area of the tumor surface) captured by digital picture and measured using MADIP software. Measuring time: Before and 24 hours after the last CIGB-300 dose and whenever it is required by safety requirements. Biweekly during CRT and quarterly until complete 1 year after CRT. Imagenological evaluation of the lesion: Evaluation of the tumor size using Abdominal and transvaginal ultrasonography, CT scans, MRI, according to the evaluation criteria for solid tumors (RECIST). Measuring time: MRI: Before CIGB-300 treatment, 21 days after this, and after CRT quarterly until to complete 1 year. CT scans and abdominal and transvaginal ultrasonography: Before CIGB-300 treatment and one year after conventional treatment to define the presence of ganglionar metastases.

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 inferior to 19 or superior to 30. 3. Pregnancy or nursing. 4. Decompensate chronic disease (arterial hypertension, diabetes mellitus, chronic renal disease, cardiac insufficiency,hyperthyroidism, malignant neoplasia, epilepsy, severe mental depression). 5. Patients with previous diagnosis of coagulation dysfunctions and other decompensate chronic hematopahies (hemophilia, leukemia, among other). 6. Clinical laboratory values outside their 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, or Bronchitis and persistent Bronchial Asthma. 9. Febrile illness (temperature >37.8°C) at the moment 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 their informed consent or to 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.

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:

Other

Other design:

Sequential

Phase:

Target sample size:

It was expected to include a minimum of 8 and a maximum of 20 patients.

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:

Lidia Idania Idrian María Yaleisys

Last Name:

González-Méndez, MD Baladron-Castrillo, MD García-García, MSc Dolores-Castro, MD Rosales-Pantoja, BSc

Affiliation:

Center for Genetic Engineering and Biotechnology

Postal Address:

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

City:

Havana

Country:

Cuba

Zip Code:

6332

Telephone:

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

Email :

lidia.gonzalez@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:

Lidia Idania Idrian María Yaleisys

Last Name:

González-Méndez, MD Baladron-Castrillo, MD García-García, MSc Dolores-Castro, MD Rosales-Pantoja, BSc

Affiliation:

Center for Genetic Engineering and Biotechnology

Postal Address:

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

City:

Havana

Country:

Cuba

Zip Code:

6332

Telephone:

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

Email :

lidia.gonzalez@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:

RPCEC00000152

Date of Registration in Primary Registry:

2013-05-16

Record Verification Date:

2013-05-07

Next update date:

2014-05-07

Link to the spanish version:

Click here [3]