Cetuximab (ERBITUX®) Added to Two Concurrent Chemoradiotherapy Platforms in Locally Advanced Head and Neck Cancer

Phase 2

Completed

Conditions: Head and Neck Cancer

Interventions: Drug: Cetuximab
Drug: 5-FU
Drug: Cisplatin
Radiation: Accelerated fraction radiotherapy with concomitant boost
Drug: Hydroxyurea
Radiation: Twice-daily radiation

Registration Number: NCT00468169

Lead Sponsor: University of Chicago

Brief Summary: The main purpose of this study is to explore and compare the efficacy of Cetuximab (ERBITUX®) added to two concurrent chemoradiotherapy platforms of different intensity in locally advanced head and neck cancer.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

Inclusion Criteria

Age 18 or older
Stage III and IV head and neck cancer
Patients with squamous cell carcinoma of unknown primary and suspected origin in the head and neck area
No prior chemotherapy or radiotherapy
Prior surgical therapy of incisional or excisional biopsy and organ-sparing procedures only
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
Normal organ and marrow function

Exclusion Criteria

Unequivocal demonstration of metastatic disease
Known severe hypersensitivity to drugs used in the study
Treatment with a non-approved or investigational drug within 30 days before Day 1
Incomplete healing from previous surgery
Pregnancy or breast feeding
Uncontrolled intercurrent illness including
Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF
Acute hepatitis or known HIV
Severe baseline neurologic deficits
Prior therapy which specifically and directly targets the EGFR pathway
Prior severe infusion reaction to a monoclonal antibody

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: Cetuximab+FHX	Twice-daily radiation	Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
B: Cetuximab + PX	Accelerated fraction radiotherapy with concomitant boost	Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 \& 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.
A: Cetuximab+FHX	5-FU	Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
A: Cetuximab+FHX	Cetuximab	Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
A: Cetuximab+FHX	Hydroxyurea	Cetuximab \[250mg/m2 (day 1, weekly x10)\] + FHX (5-FU \[CI: 600mg/m2/day; days 0-5 (120h total) every other week x5\], Hydroxyurea \[500 mg PO BID, days 0-5 (=11 doses), every other week x5\] and twice-daily radiation \[150 cGy per fraction - days 1-5, every other week x5 (70-72 Gy total dose)\]). Total duration is 10 weeks.
B: Cetuximab + PX	Cetuximab	Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 \& 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.
B: Cetuximab + PX	Cisplatin	Cetuximab \[250 mg/m2 (day 1, weekly x7)\] + PX (Cisplatin \[100mg/m2 (week 1 \& 4 on day 1 (or 2))\], Accelerated fraction radiotherapy with concomitant boost \[AFX-CB (72 Gy/42 F/6 W) (3-D or IMRT based)\]). Total duration: 7 weeks.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	2 years	Time from randomization until disease progression or death from any cause. Kaplan-Meier estimate of PFS at 2 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate to CRT	From date of chemoradiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 weeks	Response to CRT was assessed by determining whether there was evidence of residual disease in the primary site via radiographic and clinical examination.
Overall Survival (OS)	2 years	Time from randomization until death from any cause. Kaplan-Meier estimate of OS at 2 years.
Objective Response Rate to Induction	Post-Induction (8 weeks)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Residual Lymph Node Disease	Up to 10 weeks	Response to CRT was also assessed by determining if there was evidence of residual lymph node disease by neck dissection, if warranted by the presence of any radiographically large (\>1.5 cm) or focally abnormal lymph node.