A Monoclonal Antibody, Nimotuzumab, as Treatment for Recurrent or Metastatic Cervical Cancer

Phase I-II Study of Palliative Treatment With Nimotuzumab as a Second, Third Line or More of Treatment for Advanced or Metastatic Cervical Cancer

The following is an open label, non comparative, pilot study of palliative treatment as a second, third line or more of treatment in patients with recurrent, persistent or Metastatic Cervical Cancer; it has a limited sample of 15 patients with the primary goal of evaluating the response (defined as: Complete, partial or stable disease) to treatment with a Monoclonal Antibody, Nimotuzumab, on a weekly basis + CDDP 50mg/m2/BSA as a single agent every 3 weeks for patients with good renal function (Creatinine clearance => 60) or Gemcitabine 800 mg/m2/BSA in patients with renal failure (Creatinine clearance <60).

Secondary objectives consist of evaluating disease-free survival, overall survival and assess patient tolerance to treatment with Nimotuzumab.

Diagnostic criteria:

• Female patients in whom a diagnosis of cervical cancer of epithelial origin has been confirmed by histologic and/or radiologic assessment.
• Said patients must be in relapse or persistency after receiving first line chemo-radiotherapy and one or more lines of palliative chemotherapy.
• Karnofsky score of 80 or more.
• A CT scan will be performed in all patients to assess measurable target lesions.
• The clinical diagnosis must be evaluated by more than clinical investigator

Inclusion Criteria:

• Patients who give their written consent of participation in this study.
• Patients with recurrent or persistent cervical-uterine cancer, with local and/or systemic disease with measurable lesions, whether by physical examination, CT Scan or MRI detected at least in the previous 6 weeks. If there is only one lesion and it is less than 10 mm in length, a biopsy confirmation is required.
• Patients currently receiving a second, third line or more of palliative chemotherapy diagnosed at least 30 days after the last chemotherapy.
• Patients with one of the following Histopathological reports: Squamous Cell Carcinoma (epidermoid carcinoma), adenocarcinoma, adenosquamous carcinoma or glassy cell carcinoma.
• Patients must be older than 18 years old.
• ECOG score no worst than 3.
• Patients with life expectancy greater than 4 weeks.
• Patients with left ventricle ejection fraction (LVEF) ≥ 50 measured by radioisotopic ventriculography.
• Patients who meet all previous criteria with previously radiated metastatic disease in the central nervous system will be included.
• Patients with normal functioning of the bone marrow and other organs as defined by the following parameters:
• Hemoglobin ≥ 9 g/L
• Leucocytes ≥ 4000/microL
• Absolute neutrophil count ≥ 1500/microL
• Platelet count ≥ 100000/microL
• Total serum Bilirubin: up to 1.5 times the normal value
• Total Proteins: Within normal limits
• AST and ALT =/< 2.5 times the normal superior limit of the institutional laboratory
• Serum creatinine: within normal limits or up to 2 mg and GFR ≥ 60ml/min calculated with the Cockcroft-Gault equation.

Exclusion Criteria:

• Pregnant or nursing mothers.
• Patients with cervical-uterine cancer with a histopathological report of: small cell carcinoma and/or neuroendocrine tumor.
• Patients currently receiving another investigational onco-specific drug.
• Patients with a history of allergy to chemical substances with similar chemical composition to that of the monoclonal antibody or chemotherapeutic agents used in this study.
• Patients with non-controlled co-morbid states such as active infections, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, uncompensated diabetes and/or psychiatric illness.
• Presence of a second tumor. With the exception of those patients who have received adequate treatment for skin carcinomas (basal or squamous).
• Previous or concomitant malignancy except non-melanoma skin carcinoma.
• Social, familiar or geographic conditions that suggest poor attachment to the study.

Discontinuation of treatment criteria:

• At the patient´s request.
• Progression of disease causing worsening of the patient´s overall status in non manageable clinical conditions, (ECOG worst than 3).
• Death.
• Discontinuation of monitoring and/or loss of patient follow-up for more than 2 months.
• Severe adverse reaction grade 4 according to CTCAE.