Phase I of Biologics and Chemoradiation Therapy for Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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To determine a safe and effective doses of two biologic drugs, erlotinib and bevacizumab when used with chemotherapy and radiation therapy in advanced head and neck cancer

Detailed Description
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Locally advanced non-operative, Stage IV head and neck cancer has at best a guarded prognosis. Improvements in outcome have been achieved via the combination of chemotherapy and radiotherapy. Concurrent chemoradiotherapy is needed to optimize results, although recent data suggest a benefit from induction therapy as well. Nonetheless, despite high remission rates, most of these patients will suffer local-regional and/or distant recurrence from their disease. The proposed study will build upon the framework of chemoradiotherapy (induction plus concurrent) via the addition of a double biologic therapy. Specifically, the combination of bevacizumab and erlotinib will be used, as has been studied in other types of cancer.

Official Title
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A Phase I Study of the Combination of Chemoradiotherapy With Biologic Therapy for Advanced Head and Neck Cancer

Conditions
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Head and Neck Cancer, Parotid Gland Cancer, Thyroid Gland Cancer, Melanoma, Stage IV Head and Neck Cancer

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Docetaxel
* Drug: Bevacizumab
* Drug: Erlotinib
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced Carcinoma (epithelial malignancy) of the head and neck. This may include non-squamous carcinomas (e.g. parotid, thyroid, melanoma) in which a large portion of mucosa of the oral cavity and/or laryngopharynx is expected to be irradiated. Stage IV disease (T4Nany or TanyN2-3). Oligometastatic disease is allowable if it is asymptomatic. Measurable disease is not required; patients who have had surgical resection are eligible provided that it is felt that the likelihood of cure with conventional postoperative therapy is <40% and provided that there will be at least 28 days from the date of surgery to the start of study therapy. Performance status 0-1. Creatinine < or = 1.5 mg/dl. ANC > or = 1,800 cells/mm3. Platelets > or = 150,000 cells/mm3. Hemoglobin > or = 10 g/dl (transfusion is acceptable if needed). SGOT and/or SGPT < or = 2.5 times the upper institutional limit of normal. INR < or = 2.0. Age > or = 18 (informed consent). Exclusion Criteria: Current, recent (within 4 weeks of the Day 1, the first infusion of drug in this study) or planned participation in an experimental drug study other than this one. Poorly controlled blood pressure, defined as systolic bp > 150 and/or diastolic bp > 100 despite medication. Unstable angina. NY Heart Association (NYHA) Grade II or greater congestive heart failure. History of myocardial infarction or stroke within 6 months. Clinically significant peripheral vascular disease. Evidence of bleeding diathesis or coagulopathy. Presence of brain or spinal cord metastases. Major surgical procedure(s), open biopsy or significant traumatic injury within 28 days prior to Day 1 (1st day of study treatment) and/or anticipation of need for major surgical procedure during the course of the study. Urine protein: Creatinine ratio > or = 1.0 at screening.* Carotid artery exposure or other signs of impending carotid artery hemorrhage. History of abdominal fistula and/or gastrointestinal abdominal abscess within 6 months prior to enrollment. Serious, non-healing wound, ulcer, or bone fracture. Prior irradiation that would result in radiotherapy field overlap. Requirement for high dose oral anticoagulation (i.e., goal INR > 2.0). Mini-dose anticoagulation as may be used to assist in patency of central venous lines is acceptable. Subcutaneous Low-molecular weight heparin is allowable. No known allergies to any of the drug therapies being used in this protocol. No pregnancy, lactation or inability to use medically acceptable birth control if of childbearing potential.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>A combination of Cisplatin, Docetaxel, Bevacizumab, Erlotinib, and Radiotherapy | Drug: Cisplatin<br>* Two cycles during neoadjuvant therapy Response assessment at approximately day 36 Concurrent biochemoradiotherapy<br>* Other names: Platinol-AQ;Drug: Docetaxel<br>* Two cycles during neoadjuvant therapy Response assessment at approximately day 36 Concurrent biochemoradiotherapy<br>* Other names: Taxotere;Drug: Bevacizumab<br>* Two cycles during neoadjuvant therapy Response assessment at approximately day 36 Concurrent biochemoradiotherapy<br>* Other names: Avastin;Drug: Erlotinib<br>* Two cycles during neoadjuvant therapy (dose escalation) Response assessment at approximately day 36 Concurrent biochemoradiotherapy<br>* Other names: Tarceva;Radiation: Radiotherapy<br>* Radiotherapy begins as soon as possible following neoadjuvant chemotherapy, and continues for 7 weeks<br>* Other names: XRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bevacizumab and Erlotinib Combined with Chemoradiotherapy for the Treatment of Advanced Head and Neck Cancer | To determine if bevacizumab and erlotinib can be safely combined with chemoradiotherapy for advanced head and neck cancer. | Day 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Dose Limiting Toxicity (DTL) | To determine the appropriate dosing strategy for bevacizumab/erlotinib when combined with chemoradiotherapy for advanced head and neck cancer. | 30 days | 
| Complete Remission Rate | To obtain preliminary data on the complete remission rate for this treatment combination. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and neck cancer, Parotid gland cancer, thyroid gland cancer, melanoma, Chemoradiotherapy, bevacizumab, erlotinib