Treatment of Head & Neck Cancer With Chemotherapy and Radiation

Study Overview
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Brief Summary
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Two new cancer treatment drugs called targeted therapies will be added to standard treatment for head and neck cancer to see if an improvement can be made in the effectiveness of treatment for this type of cancer. Treatment will include chemotherapy, radiation therapy and targeted therapy taken over a period of 4 months.

Detailed Description
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In this trial, patients will receive induction treatment with combination chemotherapy(paclitaxel/carboplatin/infusional 5FU) plus bevacizumab. After 6 weeks of treatment, patients will be reevaluated and will then receive concurrent radiation therapy, chemotherapy (weekly paclitaxel),bevacizumab, and erlotinib. Induction Treatment: Paclitaxel 200mg/m2 by vein over 1-3 hours on Day 1 & Day 22 Carboplatin AUC 6.0 by vein over 1 hour on Days 1 and 22 Bevacizumab 15mg/kg by vein over 60-90 minutes on Days 1 and 22 5-FU 200mg/m2 as a 24 hour continuous infusion via pump on Days 1 through 43. Combined Modality Treatment: Radiation therapy is given daily, Monday through Friday for approximately 7 weeks. Erlotinib 150mg by mouth daily during the entire course of radiation (approximately 7 weeks) Paclitaxel 50mg/m2 by vein over 1-hour weekly for 6 weeks beginning Day 1 of radiation therapy Bevacizumab 15mg/kg by vein over 30-90 minutes on Days 50 and 71 at the same time of radiation therapy

Official Title
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A Phase II Trial of Neoadjuvant Chemotherapy Plus Bevacizumab Followed By Concurrent Chemotherapy/Bevacizumab/Erlotinib/Radiation Therapy in the Treatment of Locally Advanced Squamous Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Erlotinib
* Drug: Paclitaxel
* Drug: 5-FU
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically confirmed head & neck cancer Considered low cure rate with local therapy No prior treatment for this cancer Able to be up & about and perform self care Adequate renal and liver function Must be 18 years of age or older All patients will need an indwelling central venous access catheter Must be able to give written informed consent Exclusion Criteria: Active cancer treatment in the last 5 years Pregnant or lactating women History of stroke, transient ischemic attacks, or acute myocardial infarction within the past 6 months or any other serious cardiovascular disease History of neurological disease Recent history of blood in the sputum or vomitus Non-healing wounds, ulcer or long bone fractures History of bleeding problems or coagulation problems History of abdominal fistula, gastrointestinal perforation or intrabdominal abscess within 6 months History of uncontrolled hypertension Symptomatic peripheral vascular disease Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

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: Intervention<br>All patients initially received treatment with paclitaxel 200 mg/m2, 3 hour IV infusion days 1 and 22; carboplatin area under the curve (AUC) 6.0 IV, days 1 and 22; 5-fluorouracil (5-FU) 200 mg/m2 daily by 24-hour continuous IV infusion, days 1 to 43; bevacizumab 15 mg/kg IV infusion days 1 and 22. One to three weeks after completing neoadjuvant therapy, patients began treatment with concurrent chemoradiation, bevacizumab, and erlotinib. Radiation therapy began on day 1, with 1.8-Gy single daily doses, Monday through Friday, to a total dose of 68.4 Gy. Paclitaxel 50 mg/m2 was administered by 1-hour IV infusion on days 1 and 22. Erlotinib 150 mg by mouth daily began concurrently with radiation therapy and continued daily during the 7-week course of radiation. | Drug: Bevacizumab<br>* Induction Treatment: Paclitaxel 200mg/m2 by vein over 1-3 hours on Day 1 & Day 22 Carboplatin AUC 6.0 by vein over 1 hour on Days 1 and 22 Bevacizumab 15mg/kg by vein over 60-90 minutes on Days 1 and 22 5-FU 200mg/m2 as a 24 hour continuous infusion via pump on Days 1 through 43. Combined Modality Treatment: Radiation therapy is given daily, Monday through Friday for approximately 7 weeks. Erlotinib 150mg by mouth daily during the entire course of radiation (approximately 7 weeks) Paclitaxel 50mg/m2 by vein over 1-hour weekly for 6 weeks beginning Day 1 of radiation therapy Bevacizumab 15mg/kg by vein over 30-90 minutes on Days 50 and 71 at the same time of radiation therapy<br>* Other names: Avastin;Drug: Erlotinib<br>* Induction Treatment: Paclitaxel 200mg/m2 by vein over 1-3 hours on Day 1 & Day 22 Carboplatin AUC 6.0 by vein over 1 hour on Days 1 and 22 Bevacizumab 15mg/kg by vein over 60-90 minutes on Days 1 and 22 5-FU 200mg/m2 as a 24 hour continuous infusion via pump on Days 1 through 43. Combined Modality Treatment: Radiation therapy is given daily, Monday through Friday for approximately 7 weeks. Erlotinib 150mg by mouth daily during the entire course of radiation (approximately 7 weeks) Paclitaxel 50mg/m2 by vein over 1-hour weekly for 6 weeks beginning Day 1 of radiation therapy Bevacizumab 15mg/kg by vein over 30-90 minutes on Days 50 and 71 at the same time of radiation therapy<br>* Other names: Tarceva;Drug: Paclitaxel<br>* Neoadjuvant: 200 mg/m2 IV, 1-3 hour infusion, Days 1 and 22 Combined Modality: 50 mg/m2 IV, 1 hour IV infusion, weekly x6, beginning day 1 of radiation therapy<br>* Other names: Taxol;Drug: 5-FU<br>* Neoadjuvant: 200 mg/m2 24 hour continuous infusion days 1-43<br>* Other names: Efudex;Radiation: Radiation Therapy<br>* Combined Modality Therapy: 1.8 Gy/day, Monday-Friday, total dose 68.4 Gy<br>* Other names: RT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-Year Progression Free Survival (PFS) Probability, the Percentage of Patients Estimated to be Alive Without Worsening of Their Disease Two Years After Beginning Protocol Treatment | The percentage of patients estimated to be alive 2 years after beginning protocol treatment | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS)Probability, the Percentage of Patients Estimated to be Alive Two Years After Beginning Protocol Treatment | The Percentage of Patients Estimated to be Alive Two Years After Beginning Protocol Treatment | 24 Months |