Lapatinib and Cetuximab in Patients With Solid Tumors

NCT01184482 | Completed Phase 1 DMC

• 2 other identifiers: tykerb-itux 12010-218
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer; Lung Cancer; Head and Neck Cancer

Keywords

recurrent colorectal cancer; recurrent head and neck cancer; recurrent lung cancer; cetuximab; lapatinib

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

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

  12 months

Secondary Outcomes (4)

• response rate

  12 months

• Pharmacokinetics

  12 months

• Genetic polymorphisms

  12 months

• Genetic variations and activation status for EGFR and ErbB2 pathways

  12 months

Study Arms (1)

Cetuximab and lapatinib

EXPERIMENTAL

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

Interventions

cetuximab and lapatinib DRUG

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)

Also known as: Cetuximab: erbitux, Lapatinib: tykerb

Cetuximab and lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Georgetown University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Lung Neoplasms; Head and Neck Neoplasms

Interventions

Cetuximab; Lapatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• John F Deeken, M.D.

  Georgetown Univeristy Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 19, 2010
• Study Start: June 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: September 1, 2013
• Last Updated: October 31, 2013

Record last verified: 2013-10

Locations

US (1)