Clinical Trial VICCTHN1257
A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy followed by Standard Chemoradiation/Afatinib in HPV Negative Locally Advanced Stage III/IVa/IVb HNSCC
- Protocol No. VICCTHN1257
- Open Date: 08/30/2013
- Staging: Phase I/II
- Age Group: Adults
- Scope: National
- Objective: To determine the safety of 30mg once daily oral afatinib in combination with carboplatin AUC 6 and Paclitaxel 175mg/m2 q 21 days as an induction regimen in patients with HPV negative , AJCC stage III and IVa and IVb HNSCC of oral cavity, oropharynx, hypopharynx, and larynx.
- Disease Sites: Head/Neck
- Therapies: Chemotherapy - cytotoxic; Molecular Targeted Agents / Immunotherapy / Biologics; Radiotherapy
- Drugs: Afatinib; Carboplatin; Cisplatin; Paclitaxel
- Participating Institutions: Vanderbilt University
- National Clinical Trial ID: NCT01732640
- Secondary Protocol No: Not Specified
|Ages Eligible for Study:||18 Years and older|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
1. Patients must have a histologically confirmed diagnosis of squamous cell carcinoma, , operable or inoperable tumors, stage III (T3N0-1) and IVA-B (T1-4 N2-3M0 or T4N0-1M0) of oral cavity, oropharynx, hypopharynx and larynx. For patients with oropharynx primary,should be HPV negative or HPV+ with a > 10 pack year tobacco history or current smokers. HPVstatus determined by HPV in-situ hybridization and/or p16 immunostain (only for oropharynx primary).
2. Patients must have measurable disease of primary or nodes by both clinical and radiographic methods. To meet this criteria a lesion must be >= 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT or MRI. If radiographic exam utilizes spiral CT, a lesion must be >= 1cm in at least one dimension.
3. No prior therapy, including surgery with curative intent, chemotherapy, radiation therapy, immunotherapy, EGFR targeted therapies, or any other investigational agents.
4. Age >= 18 years.
5. ECOG performance status 0-1.
6. Patients must have normal hepatic, renal and bone marrow function.
• Absolute neutrophil count >=1,000/ mm3 Count
• Platelets >= 100,000/mm3 Count
• Total serum bilirubin =< 1.5mg/dL Level:
• AST and ALT =< 2.5 X ULN
• Alkaline Phosphatase =< 2.5 X ULN
• Total calculated creatinine clearance >= 60 mL/min
7. Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer.
8. Patients with the following within the last 6 months prior to pre-registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study.
• Congestive heart failure > NYHA Class II
• Unstable angina
• Myocardial infarction (with or without ST elevation)
9. Ability to understand and the willingness to sign a written informed consent document.
1. Any prior radiation above the clavicles.
2. Any prior invasive malignancy (unless non-melanomatous resectable skin or the DFS is 2 years or more).
3. History of allergic reactions attributed to compounds of similar chemical or biological composition to afatinib, or other agents used in study.
4. Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal ( if no lower limit of normal is defined in the institution, the lower limit is 50%)
5. Gastrointestinal tract disease resulting in an inability to take or absorb oral or enteral medication.
6. Baseline significant gastrointestinal symptoms with diarrhoea as a major symptom or a CTCAE Grade >1 diarrhoea of any etiology.
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
8. Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
9. Known pre-existing interstitial lung disease (ILD)
10. Pregnant women are excluded.