Lapatinib and Cetuximab in Patients With Solid Tumors

Colorectal Cancer Clinical Trial

— TYKERB-ITUX 1  

Official title:

A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01184482
• Other study ID #: tykerb-itux 1
• Secondary ID: 2010-218
• Status: Completed
• Phase: Phase 1
• First received: August 17, 2010
• Last updated: October 29, 2013
• Start date: June 2010
• Est. completion date: September 2013

Study information

• Verified date: October 2013
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: September 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Cancer

Intervention

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: 750 mg (3 tabs) 1000 mg (4 tabs) 1250 mg (5 tabs)

Locations

Country	Name	City	State
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Georgetown University	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose	The dose at which	12 months	Yes
Secondary	response rate	How well tumor responds to treatment as measured by RECIST criteria	12 months	No
Secondary	Pharmacokinetics	Pharmacokinetics of lapatinib as measured by weekly trough levels	12 months	No
Secondary	Genetic polymorphisms	genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted	12 months	No
Secondary	Genetic variations and activation status for EGFR and ErbB2 pathways	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	No