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
18 Years
N/A
Both
Head and Neck Cancer
Trial Information
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
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.
Inclusion 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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event-free Survival Rate at 1 Year
Outcome Description:
Event-free survival rate at 1 year was defined as the proportion of patients who did not have disease progression, primary site surgery, or death after being followed for 1 year.
Outcome Time Frame:
Assessed at 1 year.
Safety Issue:
No
Principal Investigator
Harold J. Wanebo, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Roger Williams Medical Center
Authority:
United States: Federal Government
Study ID:
CDR0000378194
NCT ID:
NCT00089297
Start Date:
December 2004
Completion Date:
February 2011
Related Keywords:
- Head and Neck Cancer
- Stage III head and neck cancer
- Stage IV head and neck cancer
- Cetuximab
- Paclitaxel
- Carboplatin
- Head and Neck Neoplasms
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