Lapatinib in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. This phase II trial is studying how well lapatinib works in treating patients with recurrent and/or metastatic head and neck cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the overall response rate in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with lapatinib. II. Determine the progression-free survival, time to progression, and overall survival of patients treated with this drug. III. Determine the toxicity of this drug in these patients. OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 cohorts according to prior epidermal growth factor receptor-targeted therapy (yes vs no). Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 40-88 patients (21-50 epidermal growth factor receptor [EGFR] inhibitor-naive patients [cohort A] and 19-38 EGFR inhibitor-pre-treated patients [cohort B]) will be accrued for this study within 4-12.6 months.

Official Title
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A Phase II Study Of GW572016 In Squamous Cell Carcinoma Of The Head And Neck (SCCHN)

Conditions
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Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Salivary Gland Squamous Cell Carcinoma, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Untreated Metastatic Squamous Neck Cancer With Occult Primary

Intervention / Treatment
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* Drug: lapatinib ditosylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma of the head and neck Recurrent and/or metastatic disease Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No more than 2 prior treatment regimens for recurrent or metastatic disease Prior chemotherapy as part of initial curative intent therapy (e.g., neoadjuvant, adjuvant, or concurrent chemotherapy) is allowed and does not count as prior therapy for recurrent or metastatic disease No known brain metastases Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 3 months Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal Creatinine normal Creatinine clearance > 60 mL/min Cardiac ejection fraction normal by echocardiogram or MUGA No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Able to swallow and retain oral or feeding tube-administered medication No malabsorption syndrome No requirement for IV alimentation No uncontrolled inflammatory gastrointestinal disease (e.g., Crohn's disease or ulcerative colitis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reaction attributed to compounds of similar chemical or biologic composition to lapatinib No other uncontrolled illness No active or ongoing infection No psychiatric illness or social situation that would preclude study compliance Prior cetuximab allowed See Disease Characteristics More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) No prior cumulative anthracycline therapy ≥ 450 mg/m^2 of doxorubicin or equivalent More than 4 weeks since prior radiotherapy No prior surgical procedure affecting absorption Recovered from prior therapy Other prior epidermal growth factor receptor inhibitors (e.g., gefitinib or erlotinib) allowed Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance in monitoring INR No concurrent CYP3A4 inhibitors or inducers No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (lapatinib ditosylate)<br>Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: lapatinib ditosylate<br>* Given orally<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate by RECIST | The 95% confidence intervals should be provided. | Up to 6 years | 
| Progression-free survival (PFS) | Will be estimated using the Kaplan-Meier method. | From start of treatment to time of disease progression, assessed up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Will be estimated using the Kaplan-Meier method. | Up to 6 years | 
| Changes in EGFR, pEGFR, HER2 | Paired t-tests or Wilcoxon signed rank tests will be performed to examine the magnitude and significance of pre-post treatment changes. To determine whether these markers are correlated with tumor response, both the baseline levels and the pre-post changes will be compared between responders and non-responders using the nonparametric, Wilcoxon rank-sum test. The correlative data will also be entered as covariates into a Cox regression model to determine whether they are predictive of progression-free and overall survival. | Baseline and 12 weeks | 
| Adverse events assessed using NCI CTCAE version 3.0 | Adverse events will be summarized by type and grade. | Up to 6 years |