Cediranib Maleate in Treating Patients With Recurrent or Newly Diagnosed Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well cediranib maleate works in treating patients with recurrent or newly diagnosed metastatic head and neck cancer. Cediranib maleate may stop the growth of head and neck cancer by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective clinical response in patients with recurrent or newly diagnosed metastatic squamous cell carcinoma of the head and neck treated with AZD2171 (cediranib maleate). SECONDARY OBJECTIVES: I. Determine the safety profile of this drug in these patients. II. Assess the early and late physiological and biological effects of this drug on tumor interstitial fluid pressure, pO2, and tumor microvasculature. III. Assess the value of potential noninvasive biomarkers of response, including plasma levels of molecules involved in angiogenesis, circulating endothelial cells and progenitor cells, and functional imaging changes before and after treatment. IV. Assess the gene expression patterns before and after treatment as predictors of clinical and biological response. OUTLINE: This is a multicenter study. Patients receive oral cediranib maleate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo dynamic contrast-enhanced CT imaging and blood collection periodically during study for research studies assessing plasma levels of angiogenic/antiangiogenic molecules, circulating endothelial cells (by flow cytometry), progenitor cells, and protein analysis of potential biomarkers.

Official Title
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Phase II Clinical Trial of AZD2171 Monotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Patients

Conditions
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Stage IV Oral Cavity Verrucous Carcinoma, Recurrent Lip and Oral Cavity Squamous Cell Carcinoma, Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary, Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Recurrent Oral Cavity Verrucous Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma, Recurrent Salivary Gland Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Laryngeal Verrucous Carcinoma, Salivary Gland Squamous Cell Carcinoma, Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary, Stage IV Hypopharyngeal Squamous Cell Carcinoma, Stage IV Laryngeal Squamous Cell Carcinoma, Stage IV Laryngeal Verrucous Carcinoma, Stage IV Lip and Oral Cavity Squamous Cell Carcinoma, Stage IV Major Salivary Gland Carcinoma, Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IV Oropharyngeal Squamous Cell Carcinoma, Tongue Carcinoma, Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

Intervention / Treatment
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* Drug: Cediranib Maleate
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous cell carcinoma of the head and neck meeting one of the following criteria: Recurrent disease Previously treated with standard curative therapy, including surgery and/or radiotherapy with or without chemotherapy Newly diagnosed metastatic disease Must be deemed incurable by all of the following: Salvage surgery Radiotherapy Measurable disease ≥ 1 cm by conventional techniques, flexible fiberoptic laryngoscopy, or examination under anesthesia No more than 2 prior conventional or investigational systemic therapies for categorically incurable local-regional or distant disease No known primary brain tumor or brain metastases ECOG performance status 0-1 Life expectancy ≥ 6 months WBC > 3,000/mm³ Absolute neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ Hemoglobin > 8 g/dL Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal Creatinine normal OR creatinine clearance > 60 mL/min Proteinuria ≤ +1 on 2 consecutive urine dipsticks taken ≥ 1 week apart Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception History of nonmelanoma skin cancer or other prior malignancy allowed provided the cancer has been in remission for > 3 years No history of allergic reaction attributed to compounds of similar chemical or biological composition to AZD2171 No hypertension (i.e., systolic blood pressure (BP) > 160 mm Hg and diastolic BP > 100 mm Hg) No history of hypertensive urgency, hypertensive emergency, or end-organ damage (i.e., thrombotic stroke, transient ischemic attacks, intracerebral hemorrhage, myocardial infarction, aortic aneurysm, or aortic dissection) QTc ≤ 500 msec (with Bazett's correction) No history of familial long QT syndrome No concurrent uncontrolled illness including, but not limited to, any of the following: Bleeding diathesis Congestive heart failure, defined as New York Heart Association (NYHA) class III-IV congestive heart failure NYHA class II congestive heart failure allowed provided there is increased monitoring Significant ECG abnormality Peripheral vascular disease Unstable angina pectoris Cardiac arrhythmia Pulmonary edema Atrioventricular (AV) conduction abnormalities Sick sinus syndrome Second- or third-degree AV block Deep venous thrombosis No nonhealing ulcers, bone fracture, or wounds No psychiatric illness or social situation that would preclude study compliance No traumatic injury within the past 7 days No known coagulopathy that increases risk of bleeding No history of clinically significant hemorrhages See Disease Characteristics Recovered from all prior therapies No prior antiangiogenic therapy No more than 2 prior chemotherapy or antineoplastic regimens for categorically incurable local-regional or distant disease At least 4 weeks since prior radiotherapy or major surgery At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) More than 30 days since prior participation in an investigational trial No other concurrent investigational agents No concurrent drugs or biologics with proarrhythmic potential No concurrent anticoagulants (e.g., warfarin) or antiplatelet agents No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent anticancer agents or therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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)<br>Patients receive oral cediranib maleate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Cediranib Maleate<br>* Given orally<br>* Other names: Recentin;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response (complete response [CR], partial response [PR], progressive disease [PD], and stable disease [SD]) as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria | Compared using logistic regression. | Baseline to day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 | Analyzed using binomial confidence intervals for these proportions. | Up to 28 days after last dose of study treatment | 
| Distant metastasis | Analyzed with binomial confidence intervals as well as Kaplan-Meier estimates for these proportions. | Every 2 courses until progression | 
| Overall survival | Analyzed with binomial confidence intervals as well as Kaplan-Meier estimates for these proportions. | Up to 28 days after last dose of study treatment | 
| Progression-free survival | Analyzed with binomial confidence intervals as well as Kaplan-Meier estimates for these proportions. | Up to 28 days after last dose of study treatment |