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

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ClinicalTrials.gov Identifier: NCT01184482
Recruitment Status : Completed
First Posted : August 19, 2010
Last Update Posted : October 31, 2013
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Georgetown University

Tracking Information
First Submitted Date  ICMJE August 17, 2010
First Posted Date  ICMJE August 19, 2010
Last Update Posted Date October 31, 2013
Study Start Date  ICMJE June 2010
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 17, 2010)
Maximum tolerated dose [ Time Frame: 12 months ]
The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01184482 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2010)
  • response rate [ Time Frame: 12 months ]
    How well tumor responds to treatment as measured by RECIST criteria
  • Pharmacokinetics [ Time Frame: 12 months ]
    Pharmacokinetics of lapatinib as measured by weekly trough levels
  • Genetic polymorphisms [ Time Frame: 12 months ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Lapatinib and Cetuximab in Patients With Solid Tumors
Official Title  ICMJE A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Lung Cancer
  • Head and Neck Cancer
Intervention  ICMJE 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:

  1. 750 mg (3 tabs)
  2. 1000 mg (4 tabs)
  3. 1250 mg (5 tabs)
Other Names:
  • Cetuximab: erbitux
  • Lapatinib: tykerb
Study Arms 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.
Intervention: Drug: cetuximab and lapatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 29, 2013)
22
Original Estimated Enrollment  ICMJE
 (submitted: August 17, 2010)
18
Actual Study Completion Date September 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01184482
Other Study ID Numbers  ICMJE tykerb-itux 1
2010-218 ( Other Identifier: Georgetown University )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Georgetown University
Study Sponsor  ICMJE Georgetown University
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Principal Investigator: John F Deeken, M.D. Georgetown Univeristy Medical Center
PRS Account Georgetown University
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP