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

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

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.

Study Overview

• Status: Completed
• Conditions: 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 Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Recurrent Squamous Cell Carcinoma of the Nasopharynx; 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; Untreated Metastatic Squamous Neck Cancer With Occult Primary; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: lapatinib ditosylate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ezra Cohen, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: December 7, 2004
• First Submitted That Met QC Criteria: December 7, 2004
• First Posted (Estimate): December 8, 2004

Study Record Updates

• Last Update Posted (Estimate): January 7, 2014
• Last Update Submitted That Met QC Criteria: January 6, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Respiratory Tract Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplastic Processes; Paranasal Sinus Diseases; Nose Diseases; Neoplasm Metastasis; Neoplasms, Squamous Cell; Nasopharyngeal Neoplasms; Nose Neoplasms; Head and Neck Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Recurrence; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Unknown Primary; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Laryngeal Diseases; Paranasal Sinus Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lapatinib
• Other Study ID Numbers: NCI-2012-02636 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); CDR0000398163; UCCRC-13394; NCI-6718; 13394A (Other Identifier: University of Chicago Comprehensive Cancer Center); 6718 (Other Identifier: CTEP)