search
Back to results

Lapatinib and Cetuximab in Patients With Solid Tumors (TYKERB-ITUX 1)

Primary Purpose

Colorectal Cancer, Lung Cancer, Head and Neck Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cetuximab and lapatinib
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring recurrent colorectal cancer, recurrent head and neck cancer, recurrent lung cancer, cetuximab, lapatinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Georgetown University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cetuximab and lapatinib

Arm Description

All patients will receive cetuximab by IB weekly and daily doses of lapatinib orally in 3 week cycles with response assessed every 2 cycles.

Outcomes

Primary Outcome Measures

Maximum tolerated dose
The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity

Secondary Outcome Measures

response rate
How well tumor responds to treatment as measured by RECIST criteria
Pharmacokinetics
Pharmacokinetics of lapatinib as measured by weekly trough levels
Genetic polymorphisms
genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted
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.

Full Information

First Posted
August 17, 2010
Last Updated
October 29, 2013
Sponsor
Georgetown University
Collaborators
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT01184482
Brief Title
Lapatinib and Cetuximab in Patients With Solid Tumors
Acronym
TYKERB-ITUX 1
Official Title
A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Lung Cancer, Head and Neck Cancer
Keywords
recurrent colorectal cancer, recurrent head and neck cancer, recurrent lung cancer, cetuximab, lapatinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cetuximab and lapatinib
Arm Type
Experimental
Arm Description
All patients will receive cetuximab by IB weekly and daily doses of lapatinib orally in 3 week cycles with response assessed every 2 cycles.
Intervention Type
Drug
Intervention Name(s)
cetuximab and lapatinib
Other Intervention Name(s)
Cetuximab: erbitux, Lapatinib: tykerb
Intervention Description
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)
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Description
The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity
Time Frame
12 months
Secondary Outcome Measure Information:
Title
response rate
Description
How well tumor responds to treatment as measured by RECIST criteria
Time Frame
12 months
Title
Pharmacokinetics
Description
Pharmacokinetics of lapatinib as measured by weekly trough levels
Time Frame
12 months
Title
Genetic polymorphisms
Description
genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted
Time Frame
12 months
Title
Genetic variations and activation status for EGFR and ErbB2 pathways
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John F Deeken, M.D.
Organizational Affiliation
Georgetown Univeristy Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Lapatinib and Cetuximab in Patients With Solid Tumors

We'll reach out to this number within 24 hrs