Sunitinib in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

Phase II Study of Sunitinib Malate in Head and Neck Squamous Cell Carcinoma

This phase II trial is studying how well sunitinib works in treating patients with recurrent and/or metastatic head and neck cancer. 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.

Study Overview

• Status: Completed
• Conditions: Recurrent Metastatic Squamous Neck Cancer With Occult Primary; 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 Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; 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; Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Intervention / Treatment: Drug: sunitinib malate

Detailed Description

OBJECTIVES:

I. Determine the overall response rate of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with sunitinib malate.

II. Determine the toxicity of this drug in these patients. III. Determine the feasibility of administering this drug to patients with ECOG performance status 2 (cohort B).

OUTLINE: This is a multicenter, cohort study.

Patients are assigned to one of two cohorts according to ECOG performance status (ECOG 0-1 [cohort A] vs ECOG 2 [cohort B]). Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 1 year.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Criteria:

• Hemoglobin >= 9 g/dL

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck:

  • Recurrent and/or metastatic disease
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques OR as >= 10 mm with spiral CT scan
• No known brain metastases
• Life expectancy >= 2 months
• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% (for patients in cohort A)
• ECOG PS 2 or Karnofsky PS 60-70% (for patients in cohort B)
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Calcium =< 12.0 mg/dL
• Bilirubin normal
• AST and ALT =< 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance >= 60 mL/min
• QTc < 500 msec

• No New York Heart Association class III or IV heart failure:

  • Patients with the following are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO/MUGA:

    • History of class II heart failure and asymptomatic on treatment
    • Prior anthracycline exposure
    • Prior central thoracic radiation that included the heart in the radiotherapy port
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions to compounds of similar chemical or biological composition to sunitinib malate
• No history of serious ventricular arrhythmia (i.e., ventricular fibrillation or ventricular tachycardia >= 3 beats in a row)
• No history of other significant ECG abnormalities
• No uncontrolled hypertension (defined as systolic blood pressure [BP] >= 140 mm Hg or diastolic BP >= 90 mm Hg)

• No condition resulting in an inability to take oral medication, including any of the following:

  • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
  • Active peptic ulcer disease
• No gastrostomy, jejunostomy, or other forms of enteral tube-feeding modalities
• No serious or nonhealing wound, ulcer, or bone fracture
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No cerebrovascular accident or transient ischemic attack within the past 12 months
• No myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
• No pulmonary embolism within the past 12 months
• No pre-existing uncontrolled thyroid abnormality (i.e., inability to maintain thyroid function within the normal range with medication)

• No uncontrolled intercurrent illness, including either of the following:

  • Ongoing or active infection
  • Psychiatric illness or social situation that would limit compliance with study requirement

• No more than two prior regimens for recurrent or metastatic disease:

  • Prior chemotherapy as part of initial curative intent therapy (e.g., neoadjuvant, adjuvant, or concurrent chemoradiotherapy) is allowed and will not count as prior therapy for recurrent or metastatic disease
• At least 4 weeks since prior major surgery
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• At least 4 weeks since prior radiotherapy
• No prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or VEGF Trap)
• No prior surgical procedure affecting absorption

• At least 7 days since prior and no concurrent use of CYP3A4 inhibitors, including any of the following:

  • Azole antifungals (e.g., ketoconazole, itraconazole)
  • Verapamil
  • Clarithromycin
  • HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir)
  • Erythromycin
  • Delavirdine
  • Diltiazem

• At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

  • Rifampin
  • Phenytoin
  • Rifabutin
  • Hypericum perforatum (St. John's wort)
  • Carbamazepine
  • Efavirenz
  • Phenobarbital
  • Tipranavir
• No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin):

Concurrent dosing of =< 2 mg of warfarin daily for prophylaxis of thrombosis is allowed; Concurrent low molecular weight heparin allowed provided prothrombin time INR is =< 1.5

• No other concurrent investigational agents

• No concurrent agents with proarrhythmic potential, including any of the following:

  • Terfenadine
  • Quinidine
  • Procainamide
  • Disopyramide
  • Sotalol
  • Probucol
  • Bepridil
  • Haloperidol
  • Risperidone
  • Indapamide
  • Flecainide
• No other concurrent anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.	Drug: sunitinib malate; Given orally; Other Names: Sutent; SU11248; sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response Rate (Complete Response [CR] and Partial Response [PR]) Using RECIST Criteria	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	While patient remains on treatment, up to 30 weeks
Feasibility of Treatment	Ability to remain on treatment without dose reduction	While patient remains on treatment, up to 30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Time to disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Up to 2 years
Overall Survival	Time from start of treatment until death from any cause.	Up to two years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ezra Cohen, University of Chicago

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: October 12, 2006
• First Submitted That Met QC Criteria: October 12, 2006
• First Posted (Estimate): October 13, 2006

Study Record Updates

• Last Update Posted (Estimate): July 25, 2014
• Last Update Submitted That Met QC Criteria: July 21, 2014
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Respiratory Tract Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplastic Processes; Paranasal Sinus Diseases; Nose Diseases; Neoplasm Metastasis; Neoplasms, Squamous Cell; Nasopharyngeal Neoplasms; Nose Neoplasms; Head and Neck Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Recurrence; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Unknown Primary; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Laryngeal Diseases; Paranasal Sinus Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: NCI-2009-00214 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); P30CA014599 (U.S. NIH Grant/Contract); 7738 (CTEP); CDR0000504024