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

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.

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