Pharmocokinetic/Pharmacodynamic (PK/PD) Study of the Combination Cetuximab/Gefitinib - Full Text View

Sponsors and Collaborators:	Harrison Clinical Research Merck KGaA AstraZeneca
Information provided by:	Harrison Clinical Research
ClinicalTrials.gov Identifier:	NCT00820417

Purpose

This is an open-label, phase 1, non-randomised, non-controlled trial, carried out in two centres on patients with advanced cancer expressing EGFR. Primary objective is the determination of the maximum tolerated dose (MTD) and recommended dose (RD) of the combination of intravenous Cetuximab and oral Gefitinib.

Condition	Intervention	Phase
Colorectal Cancer Head and Neck Cancer Non Small Cell Lung Cancer (NSCLC)	Drug: Cetuximab/Gefitinib combination and/or monotherapy	Phase I

MedlinePlus related topics: Cancer Colorectal Cancer Head and Neck Cancer

Drug Information available for: ZD1839 Immunoglobulins Globulin, Immune Cetuximab Epidermal Growth Factor Tyrosine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Uncontrolled, Pharmacokinetics/Dynamics Study
Official Title:	Phase 1 Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of the Combination of Cetuximab (C-225), a Chimeric Monoclonal Antibody Against the Epidermal Growth Factor Receptor (EGFR), and Gefitinib (ZD1839), a Selective EGFR Tyrosine Kinase Inhibitor, in Patients With Advanced Cancer

Further study details as provided by Harrison Clinical Research:

Primary Outcome Measures:

The primary objective of the study is to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of the combination intravenous Cetuximab/oral Gefitinib. [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the pharmacokinetic (PK) parameters of the combination Cetuximab/Gefitinib [ Designated as safety issue: No ]
To determine the pharmacogenomic profile of study patients and to correlate the different profiles with efficacy [ Designated as safety issue: No ]
To determine the possible correlation between activity and the polymorphisms of the EGFR measured in the blood and in the primary tumour [ Designated as safety issue: No ]
To assess the possible immune response related to cetuximab [ Designated as safety issue: No ]
To estimate signs of clinical activity (response rate according to the RECIST criteria) [ Designated as safety issue: No ]

Enrollment:	63
Study Start Date:	June 2004
Study Completion Date:	May 2008
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
a: Experimental Dose-escalation	Drug: Cetuximab/Gefitinib combination and/or monotherapy
B: Experimental Maximum tolerated dose (MTD)	Drug: Cetuximab/Gefitinib combination and/or monotherapy

Detailed Description:

Between 36 and 66 patients will be enrolled depending on the number of dose levels which can be completed. Patients will have histologically confirmed EFGR-expressing solid malignant tumours (colorectal cancer, head and neck cancer and NSCLC), which did not respond to standard therapy or for which no suitable therapy exists.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Written informed consent prior to inclusion
Confirmed histological diagnosis of non-resectable, solid, malignant, EGFR expressing tumours of the following types: colorectal cancer, head and neck cancer and non-small cell lung cancer (NSCLC). Advanced clinical stage III/IV which did not respond to standard therapy or for which no suitable therapy exists
Patients with at least one evaluable lesion (evaluable disease) by the RECIST criteria
Availability of tumour tissue, whether from primary tumour or metastasis to determine EGFR expression
Viability of establishing outpatient treatment
Effective contraception for patients of both sexes if there is a risk of conception
Karnofsky performance status greater than 70 %
Life expectancy > 12 weeks
Adequate renal function (creatinine < 1.5 x UNL), liver function (bilirubin < 1.5 x UNL, ALT/AST < 2.5 x UNL o <5 x UNL if hepatic metastasis) and adequate bone marrow (leucocytes > 3000/µl, absolute neutrophil count > 1500/µl, platelets > 100,000/µl, haemoglobin > 9 g/dl)
Patients must not have undergone chemotherapy, radiotherapy or major surgery during the 3 weeks before the beginning of the study, and they must have recovered from the relevant secondary effects of previous treatments
Patients agree to have a new biopsy after two weeks.

Exclusion Criteria:

Patients with any symptom of bowel obstruction and/or inflammatory bowel disease
Previous therapy with anti-EGFR drugs
Patients with known cerebral metastasis
Patients with known active and uncontrolled infections
Severe uncontrolled organic dysfunctions or metabolic disorders
Patients unable to give informed consent
Patients who do not wish to or who cannot undergo the specific study treatments and the study procedures
Pregnancy or breastfeeding
Patient participation in another clinical trial during the previous 30 days
Patients with known drug and/or alcohol abuse
Known hypersensitivity to chimeric MoAbs or pretreatment with MoAbs
Any other malignant tumour in the last two years or previously diagnosed malignant tumour if there is no guarantee that it is under complete control, except for suitably treated in situ cervical carcinoma or basocellular carcinoma
Known severe hypersensitivity to ZD1839 or any of the excipients of this product
Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not to be excluded)
Any unresolved chronic toxicity greater than common toxicity criteria (CTC) grade 2 from previous anticancer therapy
Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00820417

Locations

Belgium
UZ Gasthuisberg
Leuven, Belgium, 3000
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035

Sponsors and Collaborators

Harrison Clinical Research

Merck KGaA

AstraZeneca

More Information

Responsible Party:	Vall d'Hebron University Hospital ( Josep Tabernero, MD, Head, Gastrointestinal Cancer Unit, Medical Oncology Department )
Study ID Numbers:	C-225/ZD1839
Study First Received:	January 9, 2009
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00820417
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Harrison Clinical Research:

cetuximab
monoclonal
antibody
epidermal
growth
factor
receptor

EGFR
Gefitinib
tyrosine
kinase
inhibitor
advanced
cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Digestive System Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Carcinoma
Antibodies, Monoclonal
Antibodies

Digestive System Diseases
Respiratory Tract Diseases
Lung Neoplasms
Head and Neck Neoplasms
Lung Diseases
Gastrointestinal Neoplasms
Gefitinib
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Immunoglobulins
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009