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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01184482
Recruitment Status : Completed
First Posted : August 19, 2010
Last Update Posted : October 31, 2013
Information provided by (Responsible Party):
Georgetown University

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Lung Cancer Head and Neck Cancer Drug: cetuximab and lapatinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Lapatinib and Cetuximab in Patients With Solid Tumors
Study Start Date : June 2010
Actual Primary Completion Date : June 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine

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.
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

Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: 12 months ]
    The dose at which </= 1 out of 6 subjects experiences a dose limting toxicity

Secondary Outcome Measures :
  1. response rate [ Time Frame: 12 months ]
    How well tumor responds to treatment as measured by RECIST criteria

  2. Pharmacokinetics [ Time Frame: 12 months ]
    Pharmacokinetics of lapatinib as measured by weekly trough levels

  3. Genetic polymorphisms [ Time Frame: 12 months ]
    genetic polymorphisms in ABCG2, ABCB1, CYP3A4, and CYP3A5 wil be identified and counted

  4. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01184482

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United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
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Principal Investigator: John F Deeken, M.D. Georgetown Univeristy Medical Center
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Responsible Party: Georgetown University Identifier: NCT01184482    
Other Study ID Numbers: tykerb-itux 1
2010-218 ( Other Identifier: Georgetown University )
First Posted: August 19, 2010    Key Record Dates
Last Update Posted: October 31, 2013
Last Verified: October 2013
Keywords provided by Georgetown University:
recurrent colorectal cancer
recurrent head and neck cancer
recurrent lung cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action