Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

NCT ID: NCT00906360

Last Updated: 2013-07-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31

Brief Summary

This phase I trial is studying the side effects and best dose of sunitinib when given together with cetuximab and radiation therapy in treating patients with locally advanced or recurrent squamous cell carcinoma of the head and neck. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving sunitinib together with cetuximab and radiation therapy may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety, the maximum tolerated dose, and the dose limiting toxicity of sunitinib malate when administered in combination with cetuximab and radiotherapy in patients with locally advanced, recurrent, or second primary poor prognosis, high-risk squamous cell carcinoma of the head and neck.

SECONDARY OBJECTIVES:

I. To describe the toxicity profile of this regimen. II. To explore the tolerability and feasibility of sunitinib malate when administered in combination with cetuximab and radiotherapy in these patients.

III. To assess the best overall response rate (complete and partial response) after completion of treatment.

IV. To assess the locoregional control rate. V. To assess the distant control rate. VI. To assess the pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube.

OUTLINE: This is a dose-escalation study of sunitinib malate.

Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.

*NOTE: *Patients may have resection prior to enrollment on protocol provided they have high-risk features for recurrence.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic analysis of sunitinib malate and metabolites.

After completion of study treatment, patients are followed up periodically for up to 6 years.

Conditions

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; 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; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; 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 Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (enzyme inhibitor and monoclonal antibody therapy)

Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.

Group Type: EXPERIMENTAL

sunitinib malate

Intervention Type: DRUG

Given orally or by percutaneous gastrostomy tube

pharmacological study

Intervention Type: OTHER

Correlative studies

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

Undergo radiotherapy

cetuximab

Intervention Type: BIOLOGICAL

Given IV

Interventions

sunitinib malate

Given orally or by percutaneous gastrostomy tube

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

3-dimensional conformal radiation therapy

Undergo radiotherapy

Intervention Type: RADIATION

cetuximab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

SU11248; sunitinib; Sutent; pharmacological studies; 3D conformal radiation therapy; 3D-CRT; C225; C225 monoclonal antibody; IMC-C225; MOAB C225; monoclonal antibody C225

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, meeting any of the following criteria:

• Recurrent disease
• Second primary locoregional recurrence* with no clinically measurable distant disease
• Poor prognosis non-metastatic head and neck carcinoma (M0)
• Must have undergone radiotherapy as a component of prior treatment
• Not a candidate for surgical resection with curative intent

• Patients with high-risk features at resection or following resection for recurrence are eligible
• Must have locoregional tumor amenable to radiotherapy or reirradiation with curative intent

• Entire gross tumor recurrence volume must be able to be treated without exceeding a cumulative spinal cord dose of 50 Gy
• Unresected tumors must be measurable according to RECIST
• No known brain metastases
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• WBC ≥ 3,000/mm^³
• ANC > 1,500/mm³
• Platelet count > 100,000/mm³
• Total bilirubin < 1.5 times upper limit of normal (ULN)
• INR and PTT ratio < 1.5
• AST and ALT ≤ 2.5 times ULN
• Creatinine normal OR creatinine clearance > 60 mL/min
• Urine protein no more than trace
• Hematocrit ≥ 28%
• Hemoglobin ≥ 9 g/dL
• QTc < 500 msec
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• The following patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO and MUGA:

• Asymptomatic on treatment
• Prior anthracycline exposure
• Prior central thoracic radiotherapy included the heart in the radiotherapy port
• No clinical evidence of active infection of any type, including hepatitis B or C virus

• Infections controlled with therapy are allowed
• Patients with hepatitis B or C on antiviral therapy with no detectable virus are allowed
• No immune deficiency and/or HIV positivity
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate
• No gastrointestinal tract disease or condition, including any of the following, that impairs ability to retain sunitinib tablets:

• Inability to take oral medication or a requirement for IV alimentation
• Prior surgical procedures affecting absorption
• Active peptic ulcer disease
• None of the following conditions allowed:

• Serious or nonhealing wound, ulcer, or bone fracture
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial
• No active carotid artery involvement
• No history of documented thrombosis (pulmonary embolism within the past 12 months or deep vein thrombosis [DVT] within the past 6 months), known coagulopathies or thrombophilia, or evidence of DVT/thromboembolic event
• No history of the following cardiovascular conditions :

• Myocardial infarction within the past 12 months
• Cardiac arrhythmia or serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia ≥ 3 beats in a row) within the past 12 months
• Stable/unstable angina within the past 12 months
• Symptomatic congestive heart failure within the past 12 months
• Coronary/peripheral artery bypass graft or stenting within the past 12 months
• No cerebral vascular disease, cerebrovascular accident (stroke), or transient ischemic attack within the past 6 months
• QTc prolongation (QTc interval ≥ 500 msec)
• New York Heart Association class III-IV congestive heart failure
• Poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
• Other significant ECG abnormalities
• See Disease Characteristics
• Recovered from all prior radiotherapy and chemotherapy
• More than 4 months since prior radiotherapy to the head and neck
• More than 2 weeks since prior hormone replacement therapy or hormonal contraceptives
• More than 4 weeks since prior and no other concurrent investigational agents
• At least 1 month since prior surgery (unless ambulatory within 48 hours)
• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

• Azole antifungals (ketoconazole, itraconazole)
• Clarithromycin
• Erythromycin
• Diltiazem
• Verapamil
• HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir)
• Delavirdine
• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

• Rifampin
• Rifabutin
• Carbamazepine
• Phenobarbital
• Phenytoin
• St. John wort
• Efavirenz
• Tipranavir
• Concurrent coumarin-derivative anticoagulants (e.g., warfarin up to 2 mg daily) allowed for prophylaxis of thrombosis
• Concurrent use of medications known to affect the conductive system (e.g., beta-blockers, calcium channel blockers, or digoxin) allowed under investigator supervision
• No concurrent agent with proarrhythmic potential, including any of the following:

• Terfenadine
• Quinidine
• Procainamide
• Disopyramide
• Sotalol
• Probucol
• Bepridil
• Haloperidol
• Risperidone
• Indapamide
• Flecainide
• No concurrent chronic steroid treatment for > 6 months (i.e., prednisolone doses > 10 mg/day or equivalent)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent amifostine
• No concurrent commercial agent or therapy intended to treat head and neck cancer
• No other concurrent anticancer therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victoria Villaflor

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

Evanston CCOP-NorthShore University HealthSystem

Evanston, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc - State Boulevard

Fort Wayne, Indiana, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

University of Michigan University Hospital

Ann Arbor, Michigan, United States

Saint John's Mercy Medical Center

St Louis, Missouri, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

UCIRB 16051B

Identifier Type: -

Identifier Source: secondary_id

CDR0000601544

Identifier Type: -

Identifier Source: secondary_id

UCIRB-16051B

Identifier Type: -

Identifier Source: secondary_id

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00279

Identifier Type: -

Identifier Source: org_study_id