Saracatinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying the how well saracatinib works in treating patients with metastatic or recurrent head and neck cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the median progression-free survival for patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNSCC) treated with AZD0530 (saracatinib). SECONDARY OBJEC TIVES: I. To determine overall survival for patients with advanced or recurrent HNSCC treated with AZD0530. II. To determine objective response rate for patients with advanced or recurrent HNSCC treated with AZD0530. III. For patients with accessible tumors, to perform pre and post-treatment biopsies to assess the pharmacodynamic effects of AZD0530 on c-Src and downstream signaling molecules STAT3 and STAT5. OUTLINE: Patients receive saracatinib orally (PO) or by percutaneous endoscopic gastrostomy (PEG) tube once daily (QD) on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 weeks and then periodically thereafter.

Official Title
-----------------
A Phase II Study of AZD0530 for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Conditions
-----------------
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer

Intervention / Treatment
-----------------
* Drug: saracatinib
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma of the head and neck Persistent, recurrent, or metastatic disease that is not amenable to curative-intent therapy with surgery or radiation Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral computed tomography (CT) scan Karnofsky performance status ≥ 60% White blood cell (WBC) ≥ 3,000/mcL Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Hemoglobin > 9 g/dL Total bilirubin within upper institutional limits of normal (ULN) Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 2.5 x ULN Creatinine within ULN OR creatinine clearance ≥ 60 mL/min Patients must agree to use adequate birth control for the duration of study participation and for at least 8 weeks after discontinuation of study drug May have received 1 prior cytotoxic chemotherapy regimen for recurrent or metastatic disease Exclusion Criteria: Known brain metastases History of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530 Urine protein: creatinine ratio ≥ 1.0 OR 24-hour urine protein ≥ 1,000 mg QTc prolongation ≥ 480 msecs Intercurrent symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia History of myocardial infarction within the past year Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or breastfeeding women Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy Pulmonary fibrosis ≥ grade 2, pleural effusion (non-malignant) ≥ grade 2, or pneumonitis/pulmonary infiltrates ≥ grade 2 Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier Use of specifically prohibited cytochrome P450 3A4 (CYP3A4)-active agents or substances Prohibited drugs should be discontinued 7 days prior to the administration of the first dose of AZD0530 and for 7 days following discontinuation of AZD0530 Patients receiving any other investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (enzyme inhibitor therapy)<br>Patients receive saracatinib PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. | Drug: saracatinib<br>* Given PO<br>* Other names: AZD0530;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Response was determined as inicated in the protocol. | From the start of treatment for up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The Kaplan-Meier method will be used to estimate overall survival. | Up to 12 weeks |