Phase I of Biologics and Chemoradiation Therapy for Advanced Head and Neck Cancer
Study Details
Study Description
Brief Summary
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
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Treatment A combination of Cisplatin, Docetaxel, Bevacizumab, Erlotinib, and Radiotherapy |
Drug: Cisplatin
Two cycles during neoadjuvant therapy
Response assessment at approximately day 36
Concurrent biochemoradiotherapy
Other Names:
Drug: Docetaxel
Two cycles during neoadjuvant therapy
Response assessment at approximately day 36
Concurrent biochemoradiotherapy
Other Names:
Drug: Bevacizumab
Two cycles during neoadjuvant therapy
Response assessment at approximately day 36
Concurrent biochemoradiotherapy
Other Names:
Drug: Erlotinib
Two cycles during neoadjuvant therapy (dose escalation)
Response assessment at approximately day 36
Concurrent biochemoradiotherapy
Other Names:
Radiation: Radiotherapy
Radiotherapy begins as soon as possible following neoadjuvant chemotherapy, and continues for 7 weeks
Other Names:
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Outcome Measures
Primary Outcome Measures
- Bevacizumab and Erlotinib Combined with Chemoradiotherapy for the Treatment of Advanced Head and Neck Cancer [Day 36]
To determine if bevacizumab and erlotinib can be safely combined with chemoradiotherapy for advanced head and neck cancer.
Secondary Outcome Measures
- Determination of Dose Limiting Toxicity (DTL) [30 days]
To determine the appropriate dosing strategy for bevacizumab/erlotinib when combined with chemoradiotherapy for advanced head and neck cancer.
- Complete Remission Rate [6 months]
To obtain preliminary data on the complete remission rate for this treatment combination.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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Stage IV disease (T4Nany or TanyN2-3).
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"Oligometastatic" disease is allowable if it is asymptomatic.
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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.
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Performance status 0-1.
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Creatinine < or = 1.5 mg/dl.
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ANC > or = 1,800 cells/mm3.
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Platelets > or = 150,000 cells/mm3.
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Hemoglobin > or = 10 g/dl (transfusion is acceptable if needed).
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SGOT and/or SGPT < or = 2.5 times the upper institutional limit of normal.
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INR < or = 2.0.
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Age > or = 18 (informed consent).
Exclusion Criteria:
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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.
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Poorly controlled blood pressure, defined as systolic bp > 150 and/or diastolic bp > 100 despite medication.
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Unstable angina.
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NY Heart Association (NYHA) Grade II or greater congestive heart failure.
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History of myocardial infarction or stroke within 6 months.
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Clinically significant peripheral vascular disease.
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Evidence of bleeding diathesis or coagulopathy.
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Presence of brain or spinal cord metastases.
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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.
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Urine protein: Creatinine ratio > or = 1.0 at screening.*
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Carotid artery exposure or other signs of impending carotid artery hemorrhage.
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History of abdominal fistula and/or gastrointestinal abdominal abscess within 6 months prior to enrollment.
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Serious, non-healing wound, ulcer, or bone fracture.
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Prior irradiation that would result in radiotherapy field "overlap."
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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.
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No known allergies to any of the drug therapies being used in this protocol.
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No pregnancy, lactation or inability to use medically acceptable birth control if of childbearing potential.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
Sponsors and Collaborators
- Sidney Kimmel Cancer Center at Thomas Jefferson University
- Genentech, Inc.
Investigators
- Principal Investigator: Pramila Rani Anne, MD, Thomas Jefferson University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 06C.46
- 2005-58