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

January 9, 2009 updated by: Harrison Clinical Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Harrison Clinical Research

Collaborators

Merck KGaA, Darmstadt, Germany
AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2004

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

January 9, 2009

First Submitted That Met QC Criteria

January 9, 2009

First Posted (Estimate)

January 12, 2009

Study Record Updates

Last Update Posted (Estimate)

January 12, 2009

Last Update Submitted That Met QC Criteria

January 9, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C-225/ZD1839

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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