Clinical trial NCT00490061: Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Head and Neck Cancer
Carcinoma, Squamous Cell
Head and Neck Cancers
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2007-06-22
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression Free Survival
timeFrame: 2 year PFS: PFS at 2 yrs after study enrollment
Secondary outcomes:
measure: Overall Survival.
timeFrame: Two years survival rate after study enrollment
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Gainsville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: New York
country: United States
facility: Beth Israel
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Madison
country: United States
facility: University of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Stanford University
name: Quynh-Thu Le
role: PRINCIPAL_INVESTIGATOR
References: