Pharmocokinetic/Pharmacodynamic (PK/PD) Study of the Combination Cetuximab/Gefitinib

NCT00820417 | Completed Phase 1

• 1 other identifier: C-225/ZD1839
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Colorectal Cancer; Head and Neck Cancer; Non Small Cell Lung Cancer (NSCLC)

Keywords

cetuximab; monoclonal; antibody; epidermal; growth; factor; receptor; EGFR; Gefitinib; tyrosine; kinase; inhibitor; advanced; cancer

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (5)

• To determine the pharmacokinetic (PK) parameters of the combination Cetuximab/Gefitinib

• To determine the pharmacogenomic profile of study patients and to correlate the different profiles with efficacy

• To determine the possible correlation between activity and the polymorphisms of the EGFR measured in the blood and in the primary tumour

• To assess the possible immune response related to cetuximab

• To estimate signs of clinical activity (response rate according to the RECIST criteria)

Study Arms (2)

a

EXPERIMENTAL

Dose-escalation

Drug: Cetuximab/Gefitinib combination and/or monotherapy

B

EXPERIMENTAL

Maximum tolerated dose (MTD)

Drug: Cetuximab/Gefitinib combination and/or monotherapy

Interventions

Cetuximab/Gefitinib combination and/or monotherapy DRUG

B; a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Harrison Clinical Research: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• AstraZeneca: collaborator

Study Sites (2)

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 9, 2009
• First Posted: January 12, 2009
• Study Start: June 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: May 1, 2008
• Last Updated: January 12, 2009

Record last verified: 2009-01

Locations

ES (1); BE (1)