Safety and Efficacy Study of Nimotuzumab Plus Neoadjuvant and Concurrent Chemoradiotherapy to Treat Oropharynx and Hypopharynx Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficiency and safety of adding nimotuzumab to neoadjuvant and concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced squamous cell carcinoma of the oropharynx and hypopharynx.

Detailed Description
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Locoregionally advanced squamous cell carcinoma of the head and neck(LA-SCCHN) poses one of the most complex management challenges. This stage of disease is still potentially curable, but requires combined-modality therapy. Recent studies have showed that induction chemotherapy（neoadjuvant）reduced the 3-year distant relapse rate. Concurrent chemoradiotherapy(CCRT), on the other hand, has demonstrated a significant and consistent benefit in local control rates, but its impact on distant failure is inconsistent. Nimotuzumab is a novel EGFR-targeting monoclonal antibody that has the potential.to be used as a single agent or as a radio- and chemotherapy sensitizer for the treatment of SCCHN. Thus, investigators conducted a randomized, multicenter phaseⅡ study to compare the efficiency and safety of adding nimotuzumab to neoadjuvant and CCRT with neoadjuvant and CCRT in the treatment of patients with locoregionally advanced squamous cell carcinoma of the oropharynx and hypopharynx.

Official Title
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Neoadjuvant and Concurrent Chemoradiotherapy Plus Nimotuzumab in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Oropharynx and Hypopharynx

Conditions
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Oropharyngeal Cancer, Hypopharyngeal Cancer

Intervention / Treatment
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* Drug: docetaxel and cisplatin
* Radiation: IMRT
* Biological: Nimotuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent form Histologically confirmed locally advanced (stages III and IVb), squamous cell carcinoma of the oropharynx and hypopharynx The tumor mass had to be measurable Karnofsky performance status ≥70 Life expectancy estimated than 6 months Hematologic: WBC≥4×109 /L , plateletes≥100×109 /L, haemoglobin ≥100 g/L； Hepatic: AST/ALT<1.5 times upper limit of normal (ULN)；serum bilirubin<1.5 times ULN; Renal: Creatinine<1.5 times ULN； Exclusion Criteria: Known distant metastases Primary tumor and nodes received surgery(except of biopsy) Received other anti EGFR monoclonal antibody treatment Previous chemotherapy or radiotherapy Participation in other interventional clinical trials within 1 month Other malignant tumor (except of non-melanoma skin Cancer or carcinoma in situ of cervix) History of serious allergic or allergy History of Serious lung or heart disease Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: Neoadjuvant and CCRT<br> | Drug: docetaxel and cisplatin<br>* The neoadjuvant consists of docetaxel 75mg/m2 day 1 and cisplatin 75mg/m2 days 1 to 3, repeat every 3 weeks, for 2 cycles. CCRT: cisplatin 75mg/m2 is administered on day 1 of week 7,10 and 13 on current with RT<br>Radiation: IMRT<br>* IMRT is administered with chemotherapy from week 7 to week 13 GTV（primary tumor）：68-70Gy/35 38 F，once a day, 5 times per week CTV（Clinical target）：56-66Gy/30 36f，once a day, 5 times per week GTV-ln（positive neck region）：66-70Gy/33 36 F，once a day, 5 times per week CTV-ln（negative neck region）：50-54Gy/28 30F, once a day, 5 times<br>* Other names: CCRT;|
| Experimental: Neoadjuvant and CCRT and Nimotuzumab<br> | Drug: docetaxel and cisplatin<br>* The neoadjuvant consists of docetaxel 75mg/m2 day 1 and cisplatin 75mg/m2 days 1 to 3, repeat every 3 weeks, for 2 cycles. CCRT: cisplatin 75mg/m2 is administered on day 1 of week 7,10 and 13 on current with RT<br>Radiation: IMRT<br>* IMRT is administered with chemotherapy from week 7 to week 13 GTV（primary tumor）：68-70Gy/35 38 F，once a day, 5 times per week CTV（Clinical target）：56-66Gy/30 36f，once a day, 5 times per week GTV-ln（positive neck region）：66-70Gy/33 36 F，once a day, 5 times per week CTV-ln（negative neck region）：50-54Gy/28 30F, once a day, 5 times<br>* Other names: CCRT;Biological: Nimotuzumab<br>* Nimotuzumab was administered 200 mg IV over 1 hour on day 1,once a week, for 13 14 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Objective Response Rate: Complete response (CR)+ partial response (PR) rates base on RECIST evaluation system. | 3 months after all the treatment ending | 
| The Number of Participants with Adverse Events | Record the Number of participants with adverse events and the Grades of the AE according to CTCAE v3.0 as the two measure of safety. | Participants will be followed during the treatment and 3 months after all the treatment ending ,an expected average of 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From date of randomization until the date of death from any cause,assessed up to 5 years | 
| Progression-Free Survival |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years | 
| Evaluate the Local control Rate in 1 to 5 years. | To evaluate each year until 5 years later | Participants will be followed every year for the duration of 5 years | 
| Tumor-Free Survival |  | From date of randomization until the date of first documented occurrence of primary, neck, distant relapse,assessed up to 5 years | 
| Non-metastatic Rate |  | The time from randomization until distant relapse occur,assessed up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant, Concurrent Chemoradiotherapy,CCRT, Nimotuzumab, Locoregionally Advanced Oropharynx, Hypopharynx cancer, Randomized, Multicenter