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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Phase II Trial of Concurrent Chemoradiation With Cetuximab (ERBITUX®), 5 Fluorouracil, Hydroxyurea, and Twice-daily Radiation (CetuxFHX) Versus Cetuximab (ERBITUX®), Cisplatin, and Accelerated Radiation With Concomitant Boost (CetuxPX) After Induction Chemotherapy in Patients With Locally Advanced Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: 5-FU
* Drug: Hydroxyurea
* Radiation: Twice-daily radiation
* Drug: Cisplatin
* Radiation: Accelerated fraction radiotherapy with concomitant boost


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Cetuximab+FHX<br>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. | Drug: Cetuximab<br>* 250mg/m2(day 1, weekly x 10);<br>* Other names: Erbitux (R);Drug: 5-FU<br>* 600 mg/m2/day; days 0-5 (120 h total) every other week x 5<br>Drug: Hydroxyurea<br>* 500 mg PO BID, days 0-5 every other week x 5<br>Radiation: Twice-daily radiation<br>* 150 cGy per fraction, days 1-5, every other week x 5 (total duration 10 weeks)<br>|
| Experimental: B: Cetuximab + PX<br>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. | Drug: Cetuximab<br>* 250mg/m2(day 1, weekly x 10);<br>* Other names: Erbitux (R);Drug: Cisplatin<br>* 100 mg/m2, week 1 and 4 on day 1 (or 2)<br>Radiation: Accelerated fraction radiotherapy with concomitant boost<br>* 72 Gy/42 F/6 W (3-D or IMRT based). Total duration 7 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Kaplan-Meier estimate of PFS at 1 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. | 1 years | 
| Progression Free Survival (PFS) | 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time from randomization until death from any cause. Kaplan-Meier estimate of OS at 2 years. | 2 years | 
| Objective Response Rate to Induction | 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. | Post-Induction (8 weeks) | 
| Objective Response Rate to CRT | Response to CRT was assessed by determining whether there was evidence of residual disease in the primary site via radiographic and clinical examination. | 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 | 
| Residual Lymph Node Disease | 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. | Up to 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cetuximab, Erbitux, locally, advanced, head, neck, cancer, neoplasms, squamous, carcinoma, lymphoepithelioma