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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
63

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Harrison Clinical Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2004

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2007

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 12, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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