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

NCT ID: NCT00490061

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2016-06-30

Brief 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).

Detailed 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.

Conditions

Head and Neck Cancer; Carcinoma, Squamous Cell; Head and Neck Cancers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy and Lapatinib with DCE-MRI

DCE-MRI will precede radiotherpy before and after Lapatinib loading. 1500mg/d once daily oral Lapatinib will be administration for seven days prior to and throughout radiotherapy. Radiotherapy will be delivered as Intensity Modulated Radio Therapy (IMRT) using a G.E. Healthcare 1.5T MR, systems revision 12.0 M5 for a total dose of 70Gy delivered in 2-2.12 Gy/ fraction over the course of 6.5-7 weeks.

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

1500 mg po daily orally

Radiotherapy (radiation)

Intervention Type: PROCEDURE

Standard of Care

G.E. Healthcare 1.5T MR, systems revision 12.0 M5

Intervention Type: DEVICE

Standard of Care, used to deliver IMRT

DCE-MRI

Intervention Type: DEVICE

A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.

Interventions

Lapatinib

1500 mg po daily orally

Intervention Type: DRUG

Radiotherapy (radiation)

Standard of Care

Intervention Type: PROCEDURE

G.E. Healthcare 1.5T MR, systems revision 12.0 M5

Standard of Care, used to deliver IMRT

Intervention Type: DEVICE

DCE-MRI

A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.

Intervention Type: DEVICE

Other Intervention Names

Tykerb/Tyverb; GlaxoSmithKline; IMRT - Intensity Modulated Radiotherapy; G.E. Healthcare MRI Device and Software; Dynamic contrast-enhanced magnetic resonance imaging

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Quynh-Thu Le

OTHER

Sponsor Role: lead

Responsible Party

Quynh-Thu Le

Professor Radiation Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Quynh-Thu Le

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

University of Florida Shands Cancer Center

Gainsville, Florida, United States

Beth Israel

New York, New York, United States

Duke University

Durham, North Carolina, United States

University of Wisconsin Cancer Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

97864

Identifier Type: OTHER

Identifier Source: secondary_id

LAP #109855

Identifier Type: OTHER

Identifier Source: secondary_id

8857

Identifier Type: OTHER

Identifier Source: secondary_id

ENT0020

Identifier Type: -

Identifier Source: org_study_id