Bevacizumab and Erlotinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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This randomized phase I/II trial is to see if combining erlotinib with bevacizumab works better in treating patients who have recurrent or metastatic head and neck cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes needed for tumor cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining erlotinib with bevacizumab may kill more tumor cells.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib in patients with recurrent or metastatic head and neck cancer. II. Determine the objective response rate and stable disease/absence of early progression in patients treated with this regimen. OUTLINE: This is a dose-escalation study of bevacizumab followed by a randomized, multicenter study. Phase I: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Course 1 is 28 days in length. All subsequent courses are 21 days. Course 1: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 15 and oral erlotinib on days 1-28. Arm II: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-28. All subsequent courses: All patients receive bevacizumab as in arm II and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase I/II Study Of Bevacizumab (rhuMAb VEGF) In Combination With OSI-774 For Patients With Recurrent Or Metastatic Cancer Of The Head And Neck

Conditions
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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, Salivary Gland Squamous Cell Carcinoma, 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

Intervention / Treatment
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* Biological: bevacizumab
* Drug: erlotinib hydrochloride
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous cell cancer of the head and neck Recurrent or metastatic disease Determined to be incurable by surgery or radiotherapy Measurable disease No tumor involvement encasing or too close in proximity to a major artery or vein No known brain metastases No prior or concurrent CNS disease No primary brain tumor Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks No history of bleeding diathesis WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 INR less than 1.5 Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No significant renal impairment 24-hour urinary protein less than 0.5 g required if more than trace proteinuria at baseline No uncontrolled hypertension No symptomatic congestive heart failure No serious cardiac arrhythmia requiring medication No deep venous thrombosis No prior stroke No New York Heart Association class II-IV heart disease No grade II-IV peripheral vascular disease within the past year No arterial thromboembolic event within the past 6 months, including any of the following: Unstable angina pectoris Myocardial infarction Transient ischemic attack Cerebrovascular accident No clinically significant peripheral artery disease No significant ophthalmologic abnormalities* including any of the following: Severe dry eye syndrome Keratoconjunctivitis sicca Sjögren's syndrome Severe exposure keratopathy Disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reactions to compounds of similar chemical or biologic composition to bevacizumab or other study agents No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No significant traumatic injury within the past 28 days No other concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection requiring parenteral antibiotics No serious non-healing wound ulcer or bone fracture No seizures not controlled by standard medical therapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) More than 4 weeks since prior radiotherapy More than 4 weeks since prior major surgery More than 4 weeks since prior open biopsy Recovered from prior therapy No more than 1 prior regimen for recurrent disease No prior epidermal growth factor receptor (EGFR)-based therapy for recurrent disease No prior vascular EGFR-based therapy for recurrent disease No other concurrent investigational agents No other concurrent anticancer agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent chronic use of aspirin (325 mg/day or more) or other nonsteroidal anti-inflammatory drugs No concurrent warfarin or heparin, including low-molecular weight heparin No other concurrent or recent (within 1 month) thrombolytic agents or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive bevacizumab IV over 30-90 minutes on day 15 and oral erlotinib on days 1-28. All subsequent courses patients receive oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Drug: erlotinib hydrochloride<br>* Given orally<br>* Other names: OSI-774;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II<br>Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-28. All subsequent courses patients receive oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Drug: erlotinib hydrochloride<br>* Given orally<br>* Other names: OSI-774;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of bevacizumab when used in combination with erlotinib hydrochloride determined by dose-limiting toxicities (Phase I) |  | 28 days | 
| Objective response rate (CR + PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II) |  | Up to 6 months | 
| Progression-free survival rate (Phase II) |  | Time from the start of treatment until disease progression or death, assessed up to 7 years | 
| Overall survival rate (Phase II) |  | Up to 7 years |