- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01184482
Lapatinib and Cetuximab in Patients With Solid Tumors (TYKERB-ITUX 1)
A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors
This trial is for patients with colon cancer, head and neck cancer and lung cancer that has not responded to standard therapy.
Cetuximab targets a receptor on cancer cells called the Epidermal Growth Factor Receptor or EGFR. It is thought that this receptor is turned "on" in some cancers, enabling cancer cells to divide and grow. Blocking this receptor can turn this signal off. Cetuximab blocks this receptor from the outside of cancer cells. It is thought that cancer cells can turn this signal back on by the EGFR joining with a related receptor called ErbB2. Lapatinib blocks both EGFR and ErbB2 from the inside of cancer cells. In laboratory experiments it has been found that combining drugs that target both EGFR and ErbB2 might work better in turning this signal back off. The purpose of this study is to determine the maximum dosages that patients can tolerate when these two medicines are given at the same time.
In addition, in order to be on this trial, patients must agree to have a tumor biopsy before starting treatment on this study and 21 days after starting treatment. These biopsies are a required part of the study. Patients must also agree to have blood drawn for research testing to see whether genetic differences between patients explain different reactions to and side effects from, these medicines.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007
- Georgetown University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- At least one measurable lesion by RECIST criteria
- A tumor lesion that can be readily biopsied using a core needle via clinical exam, ultrasound, CT, or fluoroscopic-guidance
- Over the age of 18 years and able to provide informed consent
- Patients must have progressed after standard therapy for metastatic/ recurrent disease including 5-FU containing regimens for patients with colorectal cancer, and platinum-containing regimens for patients with head and neck cancer and non-small cell lung cancer.
- Patients may have received cetuximab, panitumumab or erlotinib previously
- Adequate kidney, liver, and bone marrow function
- Life expectancy greater than 3 months
- ECOG performance status </= 2
- Normal left ventricular ejection fractions
Exclusion Criteria:
- Chemotherapy or surgery within 4 weeks prior to treatment start
- Radiation treatment within 3 weeks prior to treatment start
- Prior therapy with lapatinib
- Untreated brain metastasis or neurologically unstable CNS metastases
- Any severe or uncontrolled medical condition or other condition that could affect participation in this study including unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction </= 6 months prior to study entry
- Diarrhea > grade 1 at baseline
- Patients on a medication or herbal therapy known to inhibit CYP3A4
- Gastrointestinal tract disease resulting in the inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption or active peptic ulcer disease
- Ongoing ventricular cardiac dysrhythmias of grade >/= 2
- Subjects with a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
- Serious cardiac arrhythmia requiring medication
- QTc interval > 500 msec
- Female patients who are pregnant or breast feeding, or adults who are of reproductive potential and are unwilling to refrain from conceiving a child during study treatment
- Patients unwilling or unable to comply with the protocol or provide informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cetuximab and lapatinib
All patients will receive cetuximab by IB weekly and daily doses of lapatinib orally in 3 week cycles with response assessed every 2 cycles.
|
Cetuximab: 400 mg/m2 on Day 1 then 250 mg/m2 weekly Lapatinib: Start once daily on Day 1. Dose escalating cohorts:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose
Time Frame: 12 months
|
The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
response rate
Time Frame: 12 months
|
How well tumor responds to treatment as measured by RECIST criteria
|
12 months
|
Pharmacokinetics
Time Frame: 12 months
|
Pharmacokinetics of lapatinib as measured by weekly trough levels
|
12 months
|
Genetic polymorphisms
Time Frame: 12 months
|
genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted
|
12 months
|
Genetic variations and activation status for EGFR and ErbB2 pathways
Time Frame: 12 months
|
Genetic variations and activation status for EGFR amd ErbB2 pathways will be measured in pre- and post-therapy biopsies and assessed with western blots and IHC.
|
12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: John F Deeken, M.D., Georgetown Univeristy Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Head and Neck Neoplasms
- Colorectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Cetuximab
- Lapatinib
Other Study ID Numbers
- tykerb-itux 1
- 2010-218 (Other Identifier: Georgetown University)
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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