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

Phase 2

Completed

Conditions: Recurrent Laryngeal Verrucous Carcinoma
Recurrent Lip and Oral Cavity Squamous Cell 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
Recurrent Laryngeal Squamous Cell Carcinoma

Interventions: Drug: Cediranib Maleate
Other: Laboratory Biomarker Analysis

Registration Number: NCT00458978

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

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

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (enzyme inhibitor)	Cediranib Maleate	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.
Treatment (enzyme inhibitor)	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

Name	Time	Method
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	Baseline to day 29	Compared using logistic regression.

Secondary Outcome Measures

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

Trial Locations

Locations (1): Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States

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

Recruitment & Eligibility

Study & Design

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