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

April 14, 2015 updated by: National Cancer Institute (NCI)

A Phase 2 Trial of GW572016 in Patients With Metastatic and Recurrent Squamous Cell Carcinomas of the Head and Neck

This phase II trial studies how well lapatinib ditosylate works in treating patients with metastatic or recurrent head and neck cancer. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

Status

Completed

Conditions

Detailed Description

PRIMARY OBJECTIVES:

I. The primary objective of this study is to estimate the objective response rate (complete response [CR] + partial response [PR]) in patients with squamous cell carcinomas of the head and neck following treatment with GW572016 (lapatinib ditosylate).

SECONDARY OBJECTIVES:

I. Secondary objectives of this study are to estimate time to progression, describe the adverse event profile, and to obtain preliminary assessments of changes in pre- versus post-treatment measurements for selected biomarkers in tumor cells from these patients.

OUTLINE:

Patients receive lapatinib ditosylate orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Patients must have histologically or cytologically confirmed metastatic or recurrent squamous cell carcinoma of the head/neck; these include tumors arising in the oral cavity, oropharynx, nasopharynx, hypopharynx, glottis, or ethmoid/maxillary sinus; patients with localized disease must have failed primary therapy radiotherapy, surgery, and/or chemotherapy); patients with single site or regional recurrence that, in view of the Principal Investigator (PI) or treating physician is potentially curable by resection or by re-irradiation program, must have declined such therapies
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; one or more sites of metastatic or recurrent disease must be accessible for needle biopsy
  • No more than 2 prior chemotherapy regimens; no prior treatment with tyrosine kinase inhibitors or antibodies to the epidermal growth factor receptor (EGOR) or human epidermal growth factor receptor 2 (HER2)/neu; prior chemotherapy or radiation therapy completed at least 4 weeks prior to treatment with GW572016
  • Life expectancy of greater than three months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes > 3,000/uL
  • Absolute neutrophil count > 1,500/uL
  • Platelets > 100,000/uL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or multigated acquisition (MUGA) scan; note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution
  • Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the Principal Investigator; patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring international normalized ratio (INR); if medically appropriate and treatment available, the investigator may also consider switching these patients to low molecular weight (LMW) heparin, where an interaction with GW572016 is not expected
  • The effects of GW572016 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Able to retain and absorb medication given by mouth or feeding tube

Exclusion Criteria:

  • Prior treatment:

    • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or
    • Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
    • Patients who have had prior treatment with EGFR targeting therapies
  • Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because GW572016 is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GW572016, breastfeeding should be discontinued if the mother is treated with GW572016; human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GW572016; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
  • Patients with gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
  • Concomitant requirement for medication classified as cytochrome P450 3A4 (CYP3A4) inducer or inhibitor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (lapatinib ditosylate)
Patients receive lapatinib ditosylate PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Correlative studies
Given PO
Other Names:
  • Tykerb
  • Lapatinib
  • GSK572016
  • GW-572016
  • GW2016

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of antitumor activity as measured by objective response (CR+PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: At least 6 months
Response will be classified by type and duration and 95% confidence intervals, adjusted for the interim looks, will be calculated.
At least 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events will be classified by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time Frame: Up to 12 months
At study closure, adverse events will be classified by type, grade, duration and probable relation to treatment.
Up to 12 months
Time to progression evaluated using the RECIST
Time Frame: Time from start of treatment until disease progression or date of last follow-up, up to 12 months
Product limit method will be used to estimate time to progression. We will have approximately 84% power to test the alternative with a one-sided 5% level test.
Time from start of treatment until disease progression or date of last follow-up, up to 12 months
Changes in biochemical response as measured by biomarker data
Time Frame: Up to 12 months
A proportional hazard model will be used to determine the association of selected markers with time to progression.
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Christopher Thomas, University of Virginia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

October 1, 2006

Study Registration Dates

First Submitted

June 13, 2005

First Submitted That Met QC Criteria

June 13, 2005

First Posted (Estimate)

June 14, 2005

Study Record Updates

Last Update Posted (Estimate)

April 15, 2015

Last Update Submitted That Met QC Criteria

April 14, 2015

Last Verified

November 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Tongue Cancer

Clinical Trials on laboratory biomarker analysis

Subscribe