Lapatinib and Cetuximab in Patients With Solid Tumors (TYKERB-ITUX 1)
This study is ongoing, but not recruiting participants.
Sponsor:
Georgetown University
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01184482
First received: August 17, 2010
Last updated: February 11, 2013
Last verified: February 2013
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer Lung Cancer Head and Neck Cancer |
Drug: cetuximab and lapatinib |
Phase 1 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by Georgetown University:
Primary Outcome Measures:
- 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
Secondary Outcome Measures:
- 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.
| Estimated Enrollment: | 18 |
| 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) |
| Arms | Assigned Interventions |
|---|---|
|
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:
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01184482
Locations
| United States, District of Columbia | |
| Georgetown University Medical Center | |
| Washington, District of Columbia, United States, 20007 | |
Sponsors and Collaborators
Georgetown University
GlaxoSmithKline
Investigators
| Principal Investigator: | John F Deeken, M.D. | Georgetown Univeristy Medical Center |
More Information
No publications provided
| Responsible Party: | Georgetown University |
| ClinicalTrials.gov Identifier: | NCT01184482 History of Changes |
| Other Study ID Numbers: | tykerb-itux 1, 2010-218 |
| Study First Received: | August 17, 2010 |
| Last Updated: | February 11, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Georgetown University:
|
recurrent colorectal cancer recurrent head and neck cancer recurrent lung cancer cetuximab lapatinib |
Additional relevant MeSH terms:
|
Colorectal Neoplasms Head and Neck Neoplasms Lung Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases |
Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Cetuximab Lapatinib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 17, 2013