Clinical trial NCT02095119: A Monoclonal Antibody, Nimotuzumab, as Treatment for Recurrent or Metastatic Cervical Cancer
Official title: Phase I-II Study of Palliative Treatment With Nimotuzumab as a Second, Third Line or More of Treatment for Advanced or Metastatic Cervical Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Uterine Cervical Cancer
Keywords: Uterine cervical cancer
Palliative
Treatment
Monoclonal antibody
Nimotuzumab
Lead sponsor: National Institute of Cancerología
Sponsor class: OTHER_GOV
First posted: 2014-03-24
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Antitumoral Response
timeFrame: After 4 weeks of induction therapy, and then every 3 months for a period of 2 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: After patient´s inclusion every 3 months for a period 2 years
measure: Overall Survival
timeFrame: from patient´s inclusion until 24 months
measure: Drug Toxicity
timeFrame: from patient´s inclusion every 2 weeks for a period of 2 years
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerología
state: Federal District
Study officials:
affiliation: Researcher Level D
name: Lucely Cetina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Nacional de Cancerologia de Mexico
name: Sergio A. Zapata, MD
role: STUDY_CHAIR
affiliation: Instituto Nacional de Cancerologia de Mexico
name: Roberto Jimenez, MD
role: STUDY_CHAIR
affiliation: Centro Molecular de La Habana
name: Tania Crombert, MD
role: STUDY_CHAIR
affiliation: Centro Molecular de La Habana
name: Mayra Ramos, MD
role: STUDY_CHAIR
affiliation: Pisa® Farmacéutica
name: Ezequiel Fuentes, MD
role: STUDY_CHAIR
References:
citation: Cetina L, Crombet T, Jimenez-Lima R, Zapata S, Ramos M, Avila S, Coronel J, Charco E, Bojalil R, Astudillo H, Bazan B, Duenas-Gonzalez A. A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer. Cancer Biol Ther. 2015;16(5):684-9. doi: 10.1080/15384047.2015.1026483.