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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00820417
Recruitment Status : Completed
First Posted : January 12, 2009
Last Update Posted : January 12, 2009
Merck KGaA, Darmstadt, Germany
Information provided by:
Harrison Clinical Research

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.

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Study Type : Interventional  (Clinical Trial)
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 : June 2004
Actual Primary Completion Date : September 2007
Actual Study Completion Date : May 2008

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  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 Outcome Measures :
  1. To determine the pharmacokinetic (PK) parameters of the combination Cetuximab/Gefitinib
  2. To determine the pharmacogenomic profile of study patients and to correlate the different profiles with efficacy
  3. To determine the possible correlation between activity and the polymorphisms of the EGFR measured in the blood and in the primary tumour
  4. To assess the possible immune response related to cetuximab
  5. To estimate signs of clinical activity (response rate according to the RECIST criteria)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00820417

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UZ Gasthuisberg
Leuven, Belgium, 3000
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Sponsors and Collaborators
Harrison Clinical Research
Merck KGaA, Darmstadt, Germany
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Responsible Party: Josep Tabernero, MD, Head, Gastrointestinal Cancer Unit, Medical Oncology Department, Vall d'Hebron University Hospital Identifier: NCT00820417    
Other Study ID Numbers: C-225/ZD1839
First Posted: January 12, 2009    Key Record Dates
Last Update Posted: January 12, 2009
Last Verified: January 2009
Keywords provided by Harrison Clinical Research:
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action