Nimotuzumab in Combination With TPF(Cisplatin ,Fluorouracil and Docetaxel) for Head and Neck Squamous Cell Carcinoma

Phase 2 Study of Nimotuzumab in Combination With TPF for Head and Neck Squamous Cell Carcinoma

Nimotuzumab (hR3) is an humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR). In phase II clinical trials a combination of Nimotuzumab with chemotherapy or radiation therapy achieved satisfactory therapeutic outcomes in patients with advanced squamous cell carcinoma of head and neck, or glioblastoma. We therefore postulated that Nimotuzumab in combination with conventional definitive chemotherapy might improve the rate of disease control (RDC), progression-free survival (PFS),and overall survival in patients with recurrent and/or metastatic SCCHN , which is a poor-prognosis patient population for whom there is currently no standard treatment approach, we designed this trial to test this hypothesis.

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Chemotherapy; Drug: Nimotuzumab and Chemotherapy

Detailed Description

Eligible patients were randomly assigned by using permutated blocks designed11 for each site to receive either Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen (Arm A) or docetaxel-cisplatin-fluorouracil alone regimen (Arm B). Combination arm chemotherapy was as conducted as follows. Since day 1, Nimotuzumab (200 mg, given as a 2-hour intravenous infusion before chemotherapy, Biotech Pharmaceutical Inc., Beijing, China) was administrated 1 h before chemotherapy once a week for two successive courses, followed by docetaxel (at a dose of 75 mg per square meter of body-surface area) was administered as a 1-hour intravenous infusion, followed by intravenous cisplatin (75 mg per square meter), administered during a period of 0.5 to 3 hours. After completion of the cisplatin infusion, fluorouracil (1000 mg per square meter per day) was administered as a continuous 24-hour infusion for 4 days. Patients in arm A received docetaxel-cisplatin-fluorouracil only.One treatment cycle comprised a period of 3 weeks (21 days). Patients received six cycles in both treatment arms, unless disease progression or unacceptable toxicity was observed. Patients in the experimental group who had at least stable disease could choose to continue maintenance Nimotuzumab every week until disease progression, intolerable toxicity, or study withdrawal.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • First Affiliated Hospital of Sun Yat-sen University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Institute of Stomatology of Nanjing Medical University
    • Wuxi, Jiangsu, China, 214000
      • Wuxi People's Hospital; Nanjing Medical University
    • Xuzhou, Jiangsu, China, 221009
      • Xuzhou Central Hospital of Xuzhou city,Dongnan University
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • 9th People's Hospital, School of Stomatology,Shanghai Jiaotong 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:

• Joined the study voluntary and signed informed consent form
• Age 18-75，both genders.
• Had histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck
• At least one lesions can be measured,Conventional measurements ≥2cm, computed tomography(CT) examination ≥1cm .
• Eastern Cooperative Oncology Group(ECOG) Performance Scale 0-2.
• Life expectancy of more than 3 months.
• Use of an effective contraceptive method for women when there is a risk of pregnancy during the study.
• Haemoglobin≥90g/L ,White blood cell(WBC) ≥3×10^9/L
• Hepatic function:ALAT、ASAT< 2.5 x ULN, TBIL< 1.5 x ULN
• Renal function: Creatinine < 1.5 x ULN

Exclusion Criteria:

• Received other anti EGFR monoclonal antibody treatment
• Participation in other interventional clinical trials within 1 month
• Previous received other drug or operative treatment within 6 month
• Pregnant or breast-feeding women
• History of serious allergic or allergy
• Patients with the history of Serious lung or head disease
• Other malignant tumor
• not primary tumor(except for primary tumor therapy>3months)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Chemotherapy; Chemotherapy :Docetaxel(75mg/m²,1 time/21d, 6times);Cisplatin(75mg/m²,1 time/21d, 6 times);Fluorouracil(750mg/m²/d,5times/21d, 30times)	Drug: Chemotherapy; Chemotherapy :Docetaxel(75mg/m²,1 time/21d, 6times);Cisplatin(75mg/m²,1 time/21d, 6 times);Fluorouracil(750mg/m²/d,5times/21d, 30times); Other Names: Cisplatin; Fluorouracil; Docetaxel
Experimental: Nimotuzumab and Chemotherapy; Nimotuzumab treatment:(200mg/w,18weeks ); Chemotherapy treatment: Docetaxel(75mg/m²,1 time/21d, 6times，);Cisplatin(75mg/m²,1 time/21d, 6 times);Fluorouracil(750mg/m²/d,5times/21d, 30times),Nimotuzumab treatment:(200mg/w,18weeks ).	Drug: Nimotuzumab and Chemotherapy; Nimotuzumab treatment:(200mg/w,18weeks ); Chemotherapy treatment:(Docetaxel(75mg/m²,1 time/21d, 6times);Cisplatin(75mg/m²,1 time/21d, 6 times);Fluorouracil(750mg/m²/d,5times/21d, 30times)Nimotuzumab treatment:(200mg/w,18weeks ); Other Names: Cisplatin; Fluorouracil; Docetaxel; Nimotuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Disease Control (RDC)	4years

Secondary Outcome Measures

Outcome Measure	Time Frame
toxicity, progression-free survival (PFS), and overall survival (OS).	4 years

Collaborators and Investigators

• Sponsor: Wei Guo
• Collaborators: Sun Yat-sen University
• Investigators: Study Chair: Wei Guo, MD, PhD, DDS, Dept. of Oral and Maxillofacial Surgery,9th People's Hospital, School of Stomatology,Shanghai Jiaotong University

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: August 29, 2011
• First Posted (Estimate): August 30, 2011

Study Record Updates

• Last Update Posted (Estimate): June 3, 2014
• Last Update Submitted That Met QC Criteria: June 1, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Chemotherapy; Head and Neck Squamous Cell Carcinoma; Nimotuzumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cisplatin; Fluorouracil; Nimotuzumab
• Other Study ID Numbers: BT-IST-SCCHN-008