Phase II Evaluation of Cetuximab (C225) Combined With Induction Paclitaxel and Carboplatin Followed by C225, Paclitaxel, Carboplatin, and Radiation for Stage III/IV Operable Squamous Cancer of the Head and Neck
Cetuximab
+ Carboplatin
+ Paclitaxel
Head and Neck Neoplasms
+ Neoplasms
+ Neoplasms by Site
Treatment Study
Summary
Study start date: January 6, 2005
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the effect of induction therapy comprising cetuximab, paclitaxel, and carboplatin followed by chemoradiotherapy comprising cetuximab, paclitaxel, carboplatin, and radiotherapy and maintenance therapy comprising cetuximab on 1-year event-free survival (freedom from surgery at the primary site and freedom from recurrence and death) in patients with stage III or IV operable squamous cell cancer of the head and neck. Secondary * Determine the pathologic antitumor response at the primary site in patients treated with this regimen. * Determine disease-free and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Determine local/regional and distant failure rates in patients treated with this regimen. * Determine the effect of this treatment regimen on selective biologic pathways, total and phosphorylated epidermal growth factor receptor, ERK/MAPK, and P13K/AKT in these patients. OUTLINE: This is a multicenter study. * Induction therapy (weeks 1-6): Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. During week 7 or 8, patients undergo biopsy and evaluation of the primary site. Patients then proceed to chemoradiotherapy. * Chemoradiotherapy (weeks 9-13): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 15 minutes on days 57, 64, 71, 78, and 85. Patients also undergo radiotherapy once daily, 5 days a week, on weeks 9-13. Patients with a positive biopsy at week 7 or 8 or persistent tumor at the primary site after induction therapy undergo a second biopsy after chemoradiotherapy at week 14. Patients with a negative biopsy at week 7 or 8 who achieve a complete clinical and pathological response at the primary site OR patients whose biopsy becomes negative at week 14 receive an additional 3-weeks of chemoradiotherapy beginning at week 15. Patients receive cetuximab, carboplatin, and paclitaxel as in chemoradiotherapy (as outlined above) on days 99, 106, and 113. Patients also undergo radiotherapy once daily, 5 days a week, for 3 weeks (weeks 15-17). Patients with N1-N3 disease undergo neck dissection in weeks 20-21. Patients with a positive biopsy at week 14 do not receive additional chemoradiotherapy, but rather undergo surgical resection of the primary site in weeks 18-19. Patients with N1-N3 disease also undergo neck dissection at this time. * Maintenance therapy: Beginning after completion of surgery and/or chemoradiotherapy, patients receive cetuximab IV over 1 hour once weekly for 6 months in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. ACTUAL ACCRUAL: A total of 74 patients were accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.74 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
INCLUSION CRITERIA: * Locally advanced (Stage III/IV), but potentially operable squamous cancer of the head and neck (exclude nasopharynx). Primary site biopsies must have had proven for cancer, nodal status, confirmed by clinical and pathologic exam with fine needle aspiration cytology recommended. * ECOG performance status 0 - 1. * Adequate laboratory index (ANC \> 1500/mm3, platelets \> 100,000/mm3, creatinine 1.5mg/dl, bilirubin 1.5mg/dl) completed within 4 weeks prior to registration. * Surgical resectability: * Included patients with operative stage III/IV disease, high likelihood of achieving R0 resection (complete resection with clean margins indicating NO residual cancer). * Measurable disease, biopsy proven at primary site. Patients with clinically palpable cervical nodes were to have evaluation by CT scan and fine needle aspiration (FNA) confirmation of disease. Patients with non-palpable neck nodes had CT determination. In the absence of clinically palpable nodes, radiographic findings were acceptable. * At least one objective measurable disease parameter in the primary site or neck. * Baseline measurements or evaluations must have had obtained within 4 weeks prior to registration in the study. * Age \> 18 years. * Women of childbearing potential and sexually active males were strongly advised to use an accepted and effective method of contraception. * Original diagnostic materials must have had submitted for baseline EGFR assessment by the designated laboratory. EXCLUSION CRITERIA: * Patients with fixed nodal metastases to spine or carotid artery, patients with invasion of root of tongue, pharyngeal muscle, post pharynx, or vertebral fascia or invasion of laryngeal cartilage into strap muscles or tracheal (\>1cm) invasion. * Prior chemotherapy, surgery radiation or immunotherapy for head and neck cancer. * Prior malignancies except in situ lobular breast carcinoma, in situ cervical carcinoma, basal cell cancers or previously excised and controlled cutaneous squamous cancer (\<200 mm thick) were permitted. * Significant history of cardiac disease i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias. * Prior anti-epidermal growth factor receptor antibody therapy or therapy with a tyrosine kinase inhibitor including inhibitors targeting EGFR pathway. * Prior chimerized or murine monoclonal antibody therapy or known allergy to murine proteins or cremophor EL. * Pregnant or breast-feeding women. All females of childbearing potential must have had a blood test or urine study within 72 hours of study entry and must not have had started therapy until 5 days after registration was over to rule out pregnancy.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives