A Multi-Institutional Phase II Study of Radiation and GW572016 (Lapatinib) for Patients With Stage III-IV Head and Neck Cancer Who Cannot Tolerate Concurrent Chemoradiotherapy.
18 Years
N/A
Both
Head and Neck Cancer, Carcinoma, Squamous Cell, Head and Neck Cancers
Trial Information
A Multi-Institutional Phase II Study of Radiation and GW572016 (Lapatinib) for Patients With Stage III-IV Head and Neck Cancer Who Cannot Tolerate Concurrent Chemoradiotherapy.
There is substantial data to suggest that EGFR and Her-2/neu expressions are important
predictors for prognosis in HNSCC. EGFR blockade with a monoclonal antibody in conjunction
with radiotherapy has been shown to improve survival over radiotherapy alone in patients
with locally advanced HNSCC. Dual inhibition of EGFR and ErbB2 tyrosine kinases results in
greater inhibitory effect of the downstream signaling pathways in cancer cells than
inhibition of either receptor alone. Phase I studies in HNSCC suggested that the drug is
well tolerated when delivered either alone or concurrently with cisplatin based
chemoradiotherapy in HNSCC.
We propose to combine lapatinib with RT alone in patients with locally advanced HNSCC who
cannot tolerate chemotherapy. The main objective of the study is to determine the efficacy
of combining concurrent radiation and lapatinib in terms of time-to-progression (TTP) in
this group of patients. In addition, we will determine the 2-year locoregional control rate
(LRC), progression-free survival (PFS) and overall survival (OS) in these patients. We will
also evaluate the profile and frequency of late toxicity, specifically mucosal and
dermatologic toxicity, of the combination of lapatinib and RT in patients with locally
advanced HNSCC.
Inclusion Criteria:
- Newly diagnosed stage III-IV HNSCC, pathologically confirmed (HNSCC from unknown
primary sites are allowed)
- No evidence of distant metastasis
- No prior radiation therapy to the head and neck sites.
- Able to sign a study-specific informed consent form.
- Women of childbearing potential and men with partners capable of producing offspring
must be willing to practice acceptable methods of birth control to prevent pregnancy.
- Left ventricular ejection fraction (LVEF) within the institutional normal range as
measured by ECHO (If ECHO cannot be performed or if the Investigator feels that it
is not conclusive to evaluate LVEF, then a MUGA scan should be performed).
- Having one of the following parameters that would preclude the use of concurrent CRT:
- ECOG PS > 2.
- Creatinine > 1.3 or calculate or measure creatinine clearance < 60 ml/min.
- AST or ALT > 1.5 times normal limit but < 3 times normal limit
- Total bilirubin > 1.5 mg/dL but < 3mg/dL
- History of hearing loss that would preclude cisplatin chemotherapy. These would
include the existing need of a hearing aid or a >= 25 decibel shift over 2
contiguous frequencies on a pretreatment hearing test.
- Pre-existing peripheral neuropathy that would preclude cisplatin chemotherapy
- Refuse or cannot tolerate chemotherapy
- Age 18 years or older
Exclusion Criteria:
- Known hypersensitivity to lapatinib or any of the excipients of this product
(quinazolines).
- Uncontrolled angina, arrhythmia or congestive heart failure at the time of HNSCC
diagnosis and treatment.
- History of myocardial infarction < 6 months from study entry.
- Treatment with a non-approved or investigational drug within 30 days before Day 1 of
study treatment.
- Prior treatment with EGFR or Her2/Neu directed therapies.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with Lapatinib.
- Absolute neutrophil count < 1500/uL
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Efficacy of combining lapatinib and radiotherapy in terms of time to progression (TTP) in patients with locally advanced HNSCC who cannot tolerate concurrent chemoradiotherapy
Outcome Time Frame:
Two years after completion of study
Safety Issue:
No
Principal Investigator
Quynh-Thu Le
Investigator Role:
Principal Investigator
Investigator Affiliation:
Stanford University
Authority:
United States: Institutional Review Board
Study ID:
ENT0020
NCT ID:
NCT00490061
Start Date:
July 2007
Completion Date:
July 2025
Related Keywords:
- Head and Neck Cancer
- Carcinoma, Squamous Cell
- Head and Neck Cancers
- Carcinoma
- Carcinoma, Squamous Cell
- Head and Neck Neoplasms
Name | Location |
|---|---|
| Stanford University School of Medicine | Stanford, California 94305-5317 |
| Duke University | Durham, North Carolina 27710 |
| University of Wisconsin Cancer Center | Madison, Wisconsin 53792 |
| Univerisy of Florida Shands Cancer Center | Gainsville, Florida 32610 |
| Beth Israel | New York, New York 10003 |
