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

Sponsor

Harrison Clinical Research (Industry)

Overall Status

Completed

CT.gov ID

NCT00820417

Collaborator

Merck KGaA, Darmstadt, Germany (Industry), AstraZeneca (Industry)

Enrollment

Locations

Arms

Duration (Months)

31.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Head and Neck Cancer Non Small Cell Lung Cancer (NSCLC)	Drug: Cetuximab/Gefitinib combination and/or monotherapy	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

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

Study Start Date :

Jun 1, 2004

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: a Dose-escalation	Drug: Cetuximab/Gefitinib combination and/or monotherapy
Experimental: B Maximum tolerated dose (MTD)	Drug: Cetuximab/Gefitinib combination and/or monotherapy

Arm

Intervention/Treatment

Experimental: a

Dose-escalation

Drug: Cetuximab/Gefitinib combination and/or monotherapy

Experimental: B

Maximum tolerated dose (MTD)

Drug: Cetuximab/Gefitinib combination and/or monotherapy

Outcome Measures

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. []

Secondary Outcome Measures

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) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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