Neoadjuvant Erbitux Based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer (EAGLE)

EGFR is a potential target for new anticancer therapy in head and neck squamous cell carcinoma, because blocking the EGFR by a monoclonal antibody results in inhibition of the stimulation of the receptor, therefore, in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastases. The study hypothesis is that neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy for locally advanced oral/oropharyngeal cancer could benefit the patients on prognosis. The endpoints of this study are the pathological complete response after neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy, the survival rate, and the safety.

Study Overview

• Status: Completed
• Conditions: Oral Cancer; Effects of Chemotherapy; Locally Advanced Malignant Neoplasm; Oropharyngeal Carcinoma
• Intervention / Treatment: Drug: Neo-adjuvant Erbitux-based chemotherapy

Detailed Description

The primary endpoint of this study is the pathological complete response after neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy. The second endpoint of this study is the disease free survival rates (1, 2, 3, 5 years), locoregional control rates (1, 3, 5 years), overall survival rate (3, 5 years), and the safety.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent prior to any study activities
• Age 18-75
• Histological/cytological and iconography confirmed squamous-celled oral/oropharyngeal cancer
• Stage Ⅲ/Ⅳa (T1-2, N1-2, M0 or T3-4, N0-2, M0, AJCC 2010), operable disease
• Karnofsky performance status (KPS) ≥70
• Adequate hematologic function: Neutrophils ≥1,500/mm^3, WBC >4,000/mm^3, Hb > 10 g/dL, platelet count >100,000/mm^3
• Hepatic function: ALAT/ASAT <2.5 times the upper limit of normal (ULN), bilirubin <1.5 x ULN
• Renal function: serum creatinine <1.5 x ULN
• Life expectancy ≥6 months

Exclusion Criteria:

• Evidence of distant metastatic disease and other oropharyngeal cancers
• Surgical procedure of the primary tumor or lymph nodes (except diagnostic biopsy) before study treatment
• Previous radiotherapy for the primary tumor or lymph nodes
• Previous exposure to epidermal growth factor-targeted therapy
• Prior chemotherapy or immunotherapy for the primary tumor
• Other previous malignancy within 5 years, except non-melanoma skin cancer or pre-invasive carcinoma of the cervix
• Any investigational agent prior to the 1st study medication
• Participation in another clinical study within the 30 days prior to Inclusion in this study.
• Peripheral neuropathy >grade 1
• Known grade 3 or 4 allergic reaction to any of the study treatment
• History of severe pulmonary or cardiac disease
• Creatinine Clearance <30 ml/min
• Know drug abuse /alcohol abuse
• Legal incapacity or limited legal capacity
• Active systemic infection
• Medical or psychiatric illness, which in the investigators' opinions, would not permit the subject to complete or fully and completely understand the risks and potential complications of the study
• Concurrent chronic systemic immune therapy or hormone therapy not indicated in the study protocol
• Pregnancy (confirmed by serum or urine β-HCG) or lactation period
• Severe cardiac disease such as heart failure, clinical relevant cardiac dysrhythmias, coronary artery disease or myocardial infarction within the last 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neo-adjuvant Erbitux-based chemotherapy; Neo-adjuvant Erbitus-based chemotherapy before surgery: Erbitus, Docetaxel, Cisplatin.	Drug: Neo-adjuvant Erbitux-based chemotherapy; Name/Substance: Erbitux Formulation: 2 mg/ml or 5 mg/ml Dose: 400 mg/m^2 initial, and then 250 mg/m^2 weekly Route: Intravenous infusion Frequency & treatment mode: Weekly Duration: 6 weeks Name/Substance: Docetaxel Formulation: Liquid (20 mg/2 ml) Dose: 75 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks Duration: 2 cycles (6 weeks) Name/Substance: Cisplatin Formulation: Powder (30 mg) Dose: 75 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks Duration: 2 cycles (6 weeks); Other Names: Followed by surgery and radiotherapy
NO_INTERVENTION: Surgery and radiotherapy; Surgery and post-operative radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response	To evaluate pathological Complete Response (pCR) after neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Disease Free Survival (DFS) rates (1, 2, 3, 5 years)	5 years
Locoregional Control rates	Locoregional Control rates (LCR) (1, 3, 5 years)	5 years
Overall Survival	Overall Survival (OS) rate (3, 5 years)	5 years
Number of Participants with Adverse Events	All Adverse Events(AEs),including Serious Adverse Events(SAEs), Exposure of All study drugs & radiation	5 years

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Fudan University; Tongji University; Second Military Medical University
• Investigators: Study Chair: Chen-ping Zhang, MD, PhD, Department of Oral and Maxillofacial Surger, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: September 2, 2011
• First Submitted That Met QC Criteria: September 13, 2011
• First Posted (ESTIMATE): September 14, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 21, 2017
• Last Update Submitted That Met QC Criteria: August 16, 2017
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Surgery; Radiotherapy; Oral cancer; Oropharyngeal cancer; Induction chemotherapy; Targeted chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: 9thShanghai; 10DZ1951300 (OTHER_GRANT: 10DZ1951300)