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

July 1, 2013 updated by: National Cancer Institute (NCI)

A Phase I Trial of Concurrent Chemoradiation/Chemoreirradiation With Cetuximab (ERBITUX®), Sunitinib, and Accelerated Radiation in Patients With Locally Advanced/High-risk/Recurrent Poor Prognosis Head and Neck Cancer

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Comprehensive Cancer Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Evanston, Illinois, United States, 60201
        • Evanston CCOP-NorthShore University HealthSystem
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61615
        • Illinois CancerCare-Peoria
      • Springfield, Illinois, United States, 60702
        • Central Illinois Hematology Oncology Center
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
    • Maryland
      • Baltimore, Maryland, United States, 21201-1595
        • University of Maryland Greenebaum Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan University Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63141
        • Saint John's Mercy Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert and The Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Biological: cetuximab
Given IV
Other Names:
  • C225
  • IMC-C225
  • C225 monoclonal antibody
  • MOAB C225
  • monoclonal antibody C225
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D-CRT
  • 3D conformal radiation therapy
Drug: sunitinib malate
Given orally or by percutaneous gastrostomy tube
Other Names:
  • Sutent
  • SU11248
  • sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose (MTD) of sunitinib malate
Time Frame: Up to 7-9 weeks
MTD is defined as the dose level immediately below the non-tolerated dose. The study will utilize a standard "3+3" design to determine the MTD. Dose limiting toxicities (DLTs) used for determining escalation of dose will be those occurring within the period of radiotherapy. Toxicity will be summarized by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria.
Up to 7-9 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective tumor response rates
Time Frame: From the start of the treatment to up to 6 years
Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The efficacy analysis population (an exploratory analysis of those patients on study for the MTD) will consist of all subjects who received at least 1 dose of sunitinib. Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
From the start of the treatment to up to 6 years
Locoregional control rates
Time Frame: Up to 6 years
Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
Up to 6 years
Disease control rates
Time Frame: Up to 6 years
Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
Up to 6 years
Locoregional recurrence rates
Time Frame: At 3 years
Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.
At 3 years
Time to progression
Time Frame: From the date of registration to the date of progressive disease or death from any cause
Time to progression using Kaplan-Meier product limit curves will be calculated.
From the date of registration to the date of progressive disease or death from any cause
Overall survival time
Time Frame: From the date of registration to the date of death or date of last patient contact if censored
Overall survival using Kaplan-Meier product limit curves will be calculated.
From the date of registration to the date of death or date of last patient contact if censored
Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube
Time Frame: Prior to and up to 24 hours after the start of sunitinib malate
Prior to and up to 24 hours after the start of sunitinib malate

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Victoria Villaflor, University of Chicago Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

May 20, 2009

First Submitted That Met QC Criteria

May 20, 2009

First Posted (Estimate)

May 21, 2009

Study Record Updates

Last Update Posted (Estimate)

July 2, 2013

Last Update Submitted That Met QC Criteria

July 1, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00279
  • N01CM62201 (U.S. NIH Grant/Contract)
  • UCIRB 16051B
  • CDR0000601544
  • UCIRB-16051B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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