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

Phase 2

Terminated

Conditions: Head and Neck Cancers
Head and Neck Cancer
Carcinoma, Squamous Cell

Interventions: Drug: Lapatinib
Procedure: Radiotherapy (radiation)
Device: G.E. Healthcare 1.5T MR, systems revision 12.0 M5
Device: DCE-MRI

Registration Number: NCT00490061

Lead Sponsor: Quynh-Thu Le

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiotherapy and Lapatinib with DCE-MRI	G.E. Healthcare 1.5T MR, systems revision 12.0 M5	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.
Radiotherapy and Lapatinib with DCE-MRI	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.
Radiotherapy and Lapatinib with DCE-MRI	Radiotherapy (radiation)	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.
Radiotherapy and Lapatinib with DCE-MRI	Lapatinib	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	2 year PFS: PFS at 2 yrs after study enrollment	To determine the efficacy of combining lapatinib and radiotherapy in terms of Progression-free survival (PFS) in patients with locally advanced HNSCC who cannot tolerate concurrent chemoradiotherapy. Progression-free survival is defined is the time from starting treatment to the time of first documented tumor progression or death due to any cause, which ever occurs first. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST V1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

Name	Time	Method
Overall Survival.	Two years survival rate after study enrollment	Overall survival is the time from starting treatment until death due to any cause. For subjects who do not die, time to death will be censored at the time of last contact.

Trial Locations

Locations (5): Beth Israel
🇺🇸
New York, New York, United States
Duke University
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Durham, North Carolina, United States
University of Wisconsin Cancer Center
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Madison, Wisconsin, United States
University of Florida Shands Cancer Center
🇺🇸
Gainsville, Florida, United States
Stanford University School of Medicine
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Stanford, California, United States