Phase II Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy

Head and Neck Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00490061
• Other study ID #: ENT0020
• Secondary ID: 97864LAP #109855
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 20, 2007
• Last updated: May 20, 2015
• Start date: July 2007
• Est. completion date: July 2025

Study information

• Verified date: May 2015
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

We propose to combine lapatinib with RT alone in patients with locally advanced head and neck cancer 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 head and neck squamous cell carcinoma (HNSCC).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Cancers
• Head and Neck Neoplasms

Intervention

Drug:
• Lapatinib
1500 mg po daily orally

Procedure:
• Radiotherapy
Standard of Care

Device:
• G.E. Healthcare 1.5T MR, systems revision 12.0 M5
Standard of Care

Procedure:
• Pet/CT
Standard of Care

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina
United States	Univerisy of Florida Shands Cancer Center	Gainsville	Florida
United States	University of Wisconsin Cancer Center	Madison	Wisconsin
United States	Beth Israel	New York	New York
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Quynh-Thu Le	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of combining lapatinib and radiotherapy in terms of time to progression (TTP) in patients with locally advanced HNSCC who cannot tolerate concurrent chemoradiotherapy		Two years after completion of study	No
Secondary	2-year locoregional control, progression free survival and over all survival rates in these patients		Two years after completion of study	No
Secondary	Rate and pattern of late-treatment related toxicity in these patients		Two years after completion of study (	Yes
Secondary	Role of DCE MRI in predicting treatment outcomes in treated patients Outcome Time Frame:		Two years after completion of study (	No
Secondary	Changes in the expression of relevant tumoral and circulating biomarkers		After completion of treatment (2014)	No
Secondary	Change in quality of life status relative to baseline		After completion of study	No