Lapatinib and Cetuximab in Patients With Solid Tumors (TYKERB-ITUX 1)
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.
Head and Neck Cancer
Drug: cetuximab and lapatinib
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors|
- Maximum tolerated dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity
- response rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]How well tumor responds to treatment as measured by RECIST criteria
- Pharmacokinetics [ Time Frame: 12 months ] [ Designated as safety issue: No ]Pharmacokinetics of lapatinib as measured by weekly trough levels
- Genetic polymorphisms [ Time Frame: 12 months ] [ Designated as safety issue: No ]genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted
- Genetic variations and activation status for EGFR and ErbB2 pathways [ Time Frame: 12 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||October 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
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.
Drug: cetuximab and lapatinib
Cetuximab: 400 mg/m2 on Day 1 then 250 mg/m2 weekly
Lapatinib: Start once daily on Day 1. Dose escalating cohorts:
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|Principal Investigator:||John F Deeken, M.D.||Georgetown Univeristy Medical Center|