Head and Neck Cancer
Conditions
Keywords
bevacizumab, cisplatin, cetuximab, radiation therapy, Phase II, 09-083
Brief summary
The purpose of this study is to determine the effectiveness of treatment with bevacizumab + cisplatin + cetuximab + IMRT. The doctor wishes to monitor patients for 2 years after the completion of study treatment to determine if they are cancer-free during that time. They also want to evaluate the side effects that patients experience with this treatment regimen.
Interventions
OTHERbevacizumab, cisplatin, cetuximab, radiation therapy
Patients will receive intensity-modulated radiation therapy (IMRT) in once-daily fractions. A total dose of 70Gy is planned for the primary tumor site over approximately 33 treatment days. Day 1 will refer to the first day of radiation therapy. Concurrent with radiation therapy, patients will receive cisplatin (50 mg/m2 IV on Days 1, 2 and 22, 23) and bevacizumab (15 mg/kg IV on Days 1 and 22). Cetuximab will be administered according to the Bonner regimen (4),with a loading dose approximately 7 days prior to the start of radiation therapy (400 mg/m2 IV once, on approximately Day minus 7), followed by weekly cetuximab infusions (250 mg/m2 IV weekly X 7 infusions) until the completion of radiation therapy.
Sponsors
Genentech, Inc.
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage III/IV HNSCC without distant metastasis. Patients with stage II squamous cell carcinoma of the hypopharynx will also be eligible * Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum creatinine \> 1.5 mg/dL may be eligible if calculated creatinine clearance \> or = to 55 ml/min by Cockcroft and Gault equation (or 24-hour urine collection). * Age \> or = to 18 years. * Karnofsky performance status \> or = to 70% * Adequate bone marrow function: absolute neutrophil count \> or = to 1,500/ platelets \> or = to 100,000/ul, hemoglobin \> or = to 9 gm/dl * Adequate hepatic function: Total bilirubin ≤ 1.5 X ULN (patients with Gilbert's syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 X ULN), aspartate aminotransferase (AST) ≤ 2.5 X ULN, alanine aminotransferase (ALT) ≤ 2.5 X ULN, alkaline phosphatase ≤ 2.5 X ULN. * Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * Patients must have ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Prior radiation therapy for HNSCC * Prior treatment of HNSCC with bevacizumab or other agents specifically targeting VEGF * Prior treatment of HNSCC with cetuximab or other agents specifically targeting EGFR * Other active malignancy, other than indolent malignancies, which the investigator determines are unlikely to interfere with treatment or efficacy analysis. For example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer within the no current biochemical (PSA) or radiologic evidence of disease may enroll. * Patients with nasopharyngeal carcinoma * Patients who will receive amifostine as part of the radiation treatment plan * Patients with skin breakdown/ulceration (CTCAE version 3.0, grade 2 or higher). * Patients with hearing loss requiring hearing aid or intervention (i.e. interfering in a clinically significant way with activities of daily living). * Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living). * Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) * History of unstable angina or myocardial infarction (MI) within the last year. * Urine protein: creatinine (UPC) ratio \> or = to 1.0 at screening. A random urine sample is collected. Total protein (mg/dL) and spot creatinine (mg/dL) are ordered for this sample. The UPC ratio is calculated from the results of these tests. * International normalized ratio (INR) \> 1.5 or activated partial thromboplastin time (aPTT) \> 1.5 X upper limits of normal (ULN) * Current use of warfarin, current use of heparin or low-molecular weight heparin, chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function. * Patients with gross hemoptysis or hematemesis (defined as bright red blood of 1 teaspoon of more) within 28 days prior to Day 0 protocol treatment will be excluded from this trial. Patients with incidental blood mixed with phlegm are not excluded. * Esophageal varices, non-healing ulcer, wound, or bone fracture are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the 2-year progression-free survival for patients with locally or regionally advanced HNSCC treated with concurrent IMRT + cisplatin + bevacizumab + cetuximab. | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| To determine median overall survival for patients with locally or regionally advanced HNSCC treated with concurrent IMRT + cisplatin + bevacizumab + cetuximab. | 2 years |
| To evaluate the safety and tolerability of concurrent IMRT + cisplatin + bevacizumab + cetuximab. | 2 years |
| To explore the potential utility of 18F FLT PET for early response assessment. | 2 years |
Countries
United States
Outcome results
None listed