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
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.
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.
Inclusion Criteria:
Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, meeting any of the following criteria:
Must have undergone radiotherapy as a component of prior treatment
Not a candidate for surgical resection with curative intent
Must have locoregional tumor amenable to radiotherapy or reirradiation with curative intent
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:
No clinical evidence of active infection of any type, including hepatitis B or C virus
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:
None of the following conditions allowed:
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 :
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:
At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
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:
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
Fort Wayne, Indiana 46845, United States