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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00458978

Collaborator

(none)

Enrollment

Location

Arm

88.9

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Laryngeal 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 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 Oral Cavity Verrucous Carcinoma Stage IV Oropharyngeal Squamous Cell Carcinoma Tongue Carcinoma Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary	Drug: Cediranib Maleate Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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:

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.
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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzyme inhibitor) 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 Given orally Other Names: AZD2171 AZD2171 Maleate Recentin Other: Laboratory Biomarker Analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (enzyme inhibitor)

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

Given orally

Other Names:

AZD2171

AZD2171 Maleate

Recentin

Other: Laboratory Biomarker Analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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