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

Primary Purpose

Uterine Cervical Cancer

Status

Completed

Phase

Phase 1

Locations

Mexico

Study Type

Interventional

Intervention

Nimotuzumab

Cisplatin

Gemcitabine

CT Scan

About this trial

This is an interventional treatment trial for Uterine Cervical Cancer focused on measuring Uterine cervical cancer, Palliative, Treatment, Monoclonal antibody, Nimotuzumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Instituto Nacional de Cancerología

Outcomes

Primary Outcome Measures

Antitumoral Response

Treatment response will be evaluated according to the new International Criteria from Response Evaluation Committee in Solid Tumors (RESIST). Antitumoral response will be evaluated from patient´s inclusion after 4 weeks of induction therapy and then every 3 months until second year of follow up for each patient.

Secondary Outcome Measures

Progression Free Survival

Progression Free Survival will be defined as the time elapsed since the beginning of interventions until progressive disease is documented by growth of measurable lesions or new lesions on CT Scan or MRI according to the response evaluation criteria in solid tumors (JNCI 92 (3): 205-216, 2000).

Overall Survival

Patient´s survival since inclusion until death

Drug Toxicity

Drug toxicity will be assessed with hematologic, renal and hepatic laboratory measures as well as patient symptomatology and physical findings. Any abnormality in these parameters will be reported as an adverse event according to the Common Terminology Criteria for Adverse Events version 3.0(CTCAEV3.0, 2006)

Full Information

NCT ID

NCT02095119

First Posted

February 17, 2014

Last Updated

April 13, 2015

Sponsor

National Institute of Cancerología

1. Study Identification

Unique Protocol Identification Number

NCT02095119

Brief Title

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

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Completed

Study Start Date

July 2008 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Institute of Cancerología

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Uterine Cervical Cancer

Keywords

Uterine cervical cancer, Palliative, Treatment, Monoclonal antibody, Nimotuzumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Nimotuzumab

Intervention Description

Monoclonal antibody Nimotuzumab will be administered alone at a 200mg dose weekly during the first 4 weeks. Posteriorly it will be administered with a maintenance dose of 200 mg every 2 weeks in combination with chemotherapeutic agents Cisplatin in patients with good renal function or Gemcitabine in patients with kidney failure data until exclusion or death occurs. The administration will be intravenously in 250 ml of saline solution in a time period of 30 minutes.

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cisplatin will be administered at a calculated dose of 50mg/m2/BSA every 21 days as concomitant therapy to Nimotuzumab, until 6 cycles are completed, exclusion or death occurs, only in patients whose creatinine clearance as defined by the Cockcroft-Gault equation is >/= 60. The administration form will be intravenously.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Gemcitabine will be administered at a calculated dose of 800 mg/m2/BSA every 21 days as concomitant therapy to Nimotuzumab, until 6 cycles are completed, exclusion or death occurs, in patients with kidney failure data(Creatinine clearance as defined by the Cockcroft -Gault equation < 60). The administration form will be intravenously.

Intervention Type

Procedure

Intervention Name(s)

CT Scan

Intervention Description

A CT Scan will be performed in all patients prior to the beginning of treatment to assess any measurable tumor found by this method. The CT Scan will be repeated once the patient completes the induction phase with Nimotuzumab (4 once a week doses), when the patient has completed 3 full cycles of combination therapy with Nimotuzumab (every 2 weeks)and Gemcitabine or Cisplatin (every 21 days)and once more when the patient has completed 6 full cycles of the aforementioned therapy.

Primary Outcome Measure Information:

Title

Antitumoral Response

Description

Time Frame

After 4 weeks of induction therapy, and then every 3 months for a period of 2 years

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

Time Frame

After patient´s inclusion every 3 months for a period 2 years

Title

Overall Survival

Description

Patient´s survival since inclusion until death

Time Frame

from patient´s inclusion until 24 months

Title

Drug Toxicity

Description

Time Frame

from patient´s inclusion every 2 weeks for a period of 2 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: