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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00906360
First received: May 20, 2009
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: sunitinib malate
Other: pharmacological study
Radiation: 3-dimensional conformal radiation therapy
Biological: cetuximab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) of sunitinib malate [ Time Frame: Up to 7-9 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Objective tumor response rates [ Time Frame: From the start of the treatment to up to 6 years ] [ Designated as safety issue: No ]
    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.

  • Locoregional control rates [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

  • Disease control rates [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

  • Locoregional recurrence rates [ Time Frame: At 3 years ] [ Designated as safety issue: No ]
    Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

  • Time to progression [ Time Frame: From the date of registration to the date of progressive disease or death from any cause ] [ Designated as safety issue: No ]
    Time to progression using Kaplan-Meier product limit curves will be calculated.

  • Overall survival time [ Time Frame: From the date of registration to the date of death or date of last patient contact if censored ] [ Designated as safety issue: No ]
    Overall survival using Kaplan-Meier product limit curves will be calculated.

  • Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube [ Time Frame: Prior to and up to 24 hours after the start of sunitinib malate ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: July 2008
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: sunitinib malate
Given orally or by percutaneous gastrostomy tube
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Radiation: 3-dimensional conformal radiation therapy
Undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00906360

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

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00906360     History of Changes
Other Study ID Numbers: NCI-2009-00279, UCIRB 16051B, CDR0000601544, UCIRB-16051B, N01CM62201
Study First Received: May 20, 2009
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Tongue Neoplasms
Carcinoma, Verrucous
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Hypopharyngeal Neoplasms
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Salivary Gland Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms

ClinicalTrials.gov processed this record on April 15, 2014