Safety and Pharmacology of CIGB-300 in cervical cancer (CERVIFARM-300 Study)

• Register: RPCEC
• Last refreshed on: 29 April 2013
• Main ID: RPCEC00000141
• Date of registration: 18/01/2013
• Primary sponsor: Center for Genetic Engineering and Biotechnology (CIGB)
• Public title: Safety and Pharmacology of CIGB-300 in cervical cancer (CERVIFARM-300 Study)
• Scientific title: Safety and pharmacological evaluation of the intratumoral CIGB-300 application to patients with stage IB2-II cervical cancer
• Date of first enrolment: 20/03/2008
• Target sample size: 24 (6 patients per group)
• Recruitment status: Closed
• URL: http://registroclinico.sld.cu/trials/RPCEC00000141-En
• Study type: Interventional
• Study design: Randomization: Nonrandomized Trial Blinding: Open. Placebo: Uncontrolled Assignment: Other Purpose: Treatment Other design features: Sequential dose escalation

Countries of recruitment

Cuba

Contacts

• Name: Idania Idrian Lidia Baladrón-Castrillo, MD García-García, MSc González-Méndez, MD
• Affiliation: Center for Genetic Engineering and Biotechnology (CIGB)

• Name: Idania Idrian Lidia Baladrón-Castrillo, MD García-García, MSc González-Méndez, MD
• Affiliation: Center for Genetic Engineering and Biotechnology (CIGB)

Key inclusion & exclusion criteria

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. 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.

Age minimum: 18 years
Age maximum: 75 years
Gender: Female

Health Condition(s) or Problem(s) studied

Cervical epidermoid carcinoma, stage IB2-II.

Intervention(s)

Study group (CIGB-300, 35mg). Doses of 35 mg resuspended in 2 ml of water for injection, applied by intratumor route once per day, during 5 days. Conventional chemo-radiotherapy will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology. The regimen 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, 70mg). Doses of 70 mg resuspended in 2 ml of water for injection, applied by intratumor route once per day, during 5 days. Conventional chemo-radiotherapy will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology. The regimen 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, 245mg). Doses of 245 mg resuspended in 2 ml of water for injection, applied by intratumor route once per day, during 5 days. Conventional chemo-radiotherapy will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology. The regimen 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, 490mg). Doses of 490 mg resuspended in 2 ml of water for injection, applied by intratumor route once per day, during 5 days. Conventional chemo-radiotherapy will start 25- 35 days after CIGB-300 treatment according to specific international guidelines for this pathology.

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, 16h, 24h, 36h and 48h 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, 16h, 24h, 36h and 48h after the first dose. The urine will be collected at intervals during this sampling period to determine the excreted magnitude and renal clearance. Safety variables: Presence of severe adverse events (Yes, No). Measuring time: until 24 hours after each administration. Presence of clinical Adverse Events (AE). Measuring time: until 24 hours after each administration. Then, patients will be followed during and at 3, 6, 9, and 12 months after chemo-radiotherapy. - 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, 12h and 24h after each dose. Laboratory tests (complete blood count, glucemy, creatinine, transaminases). Measuring time: At baseline, and 21 days after treatment. Later weekly during chemo-radiotherapy and each three months during a one-year follow-up. Histamine plasmatic levels ( ELISA techniques). Measuring time: At baseline, 15min and 24h after the first dose; and at any other moment if a possible histamine release was suspected.

Secondary Outcome(s)

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: At baseline and 21 days after treatment. Later each three months during a one-year follow-up after chemo-radiotherapy. Imagenological evaluation (Tumor size using abdominal and transvaginal ultrasonography, CT scans, MRI, according to the evaluation criteria for solid tumors-RECIST). Measuring time: At baseline and 21 days after treatment. Later each three months during a one-year follow-up after chemo-radiotherapy.

Secondary ID(s)

IG/CIGB300I/CC/0701

Source(s) of Monetary Support

HeberBiotec S.A. Chemo Group

Secondary Sponsor(s)

Ministry of Public Health, Cuba