Clinical trial NCT00906360: Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-05-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum-tolerated dose (MTD) of sunitinib malate
timeFrame: Up to 7-9 weeks
Secondary outcomes:
measure: Objective tumor response rates
timeFrame: From the start of the treatment to up to 6 years
measure: Locoregional control rates
timeFrame: Up to 6 years
measure: Disease control rates
timeFrame: Up to 6 years
measure: Locoregional recurrence rates
timeFrame: At 3 years
measure: Time to progression
timeFrame: From the date of registration to the date of progressive disease or death from any cause
measure: Overall survival time
timeFrame: From the date of registration to the date of death or date of last patient contact if censored
measure: Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube
timeFrame: Prior to and up to 24 hours after the start of sunitinib malate
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston CCOP-NorthShore University HealthSystem
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan University Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Saint John's Mercy Medical Center
state: Missouri
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Victoria Villaflor
role: PRINCIPAL_INVESTIGATOR
References: