Nimotuzumab in Combination With Chemoradiation for Nasopharyngeal Cancer

Sponsor

Biotech Pharmaceutical Co., Ltd. (Other)

Overall Status

Unknown status

CT.gov ID

NCT01074021

Collaborator

(none)

480

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Nimotuzumab is an IgG1 humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate nimotuzumab in different indications. Nimotuzumab has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. The Clinical efficacy has been shown in adult with head and neck cancer. The study assessed the clinical efficacy, and safety of the combination of Nimotuzumab administered concomitantly with chemotherapy and radiotherapy in patients with advanced nasopharyngeal cancer.

Condition or Disease	Intervention/Treatment	Phase
Nasopharyngeal Cancer	Drug: Nimotuzumab Drug: placebo plus chemoradiotherapy	Phase 3

Detailed Description

Patients with advanced nasopharyngeal cancer will be randomized to 2 arms. The patients in experimental arm will be treated with Nimotuzumab which will be used concurrently with radiotherapy and chemotherapy. The chemotherapy regimen were Cisplatin monotherapy. The active comparator arm will be administered chemotherapy and radiotherapy only. The dose and regimen were the same with experiment arm. The patients'hematopoietic , hepatic and renal function tests will be monitored weekly, a physical exam and reassessment of the tumor will be performed at the first and the fourth month, and followup every six months to evaluate the survival index in three years after the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

480 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Prospective,Randomized,Double-Blind,Controlled,Multicenter,Phase III Study of Nimotuzumab in Combination With Chemotherapy and Radiotherapy for Patients With Local Advanced Nasopharyngeal Cancer

Study Start Date :

Oct 1, 2009

Anticipated Primary Completion Date :

May 1, 2016

Anticipated Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nimotuzumab plus chemoradiotherapy	Drug: Nimotuzumab Nimotuzumab:(200mg/w,weekly, 7-8 weeks, one week before radiotherapy) Radiotherapy: IMRT: Nasopharynx: GTV 66-78. 2Gy,CTV1 60-64Gy,CTV2 54-60Gy.30-34 times, 2.20-2.30Gy/time,once a day, 5 days/w, 6-7 weeks. Neck: lymph node positive, GTVn 60-70Gy, once a day, 5 days/w, 6-7weeks; lymph node negative, CTVn50-55Gy, once a day, 5 days/w, 6-7 weeks. CRT: Nasopharynx, 70-(76-80)Gy, 35-(38-40)times, 2Gy/time, once a day, 5 days/w, 6-8weeks. If disease residual when radiotherapy finished could increase the dose appropriate. Neck: lymph node positive, 64-70 Gy, 32-35 times, 2 Gy/time, once a day, 5 days/w, 6-7 weeks; lymph node negative, 50-56 Gy, 25-28 times,2 Gy/time, once a day, 5 days/w, 5-6weeks cisplatin Chemotherapy: Cisplatin (100 mg/m2,1 time/21d, 3 times，on days 2, 23, 44 during the radiotherapy)
Placebo Comparator: placebo plus chemoradiotherapy	Drug: placebo plus chemoradiotherapy Placebo treatment:4 bottles/w,weekly, 7-8 weeks, one week before radiotherapy Radiotherapy: IMRT: Nasopharynx: GTV 66-78. 2Gy,CTV1 60-64Gy,CTV2 54-60Gy.30-34 times, 2.20-2.30Gy/time,once a day, 5 days/w, 6-7 weeks. Neck: lymph node positive, GTVn 60-70Gy, once a day, 5 days/w, 6-7weeks; lymph node negative, CTVn50-55Gy, once a day, 5 days/w, 6-7 weeks. CRT: Nasopharynx, 70-(76-80)Gy, 35-(38-40)times, 2Gy/time, once a day, 5 days/w, 6-8weeks. If disease residual when radiotherapy finished could increase the dose appropriate. Neck: lymph node positive, 64-70 Gy, 32-35 times, 2 Gy/time, once a day, 5 days/w, 6-7 weeks; lymph node negative, 50-56 Gy, 25-28 times,2 Gy/time, once a day, 5 days/w, 5-6weeks cisplatin Chemotherapy: Cisplatin (100 mg/m2,1 time/21d, 3 times，on days 2, 23, 44 during the radiotherapy)

Arm

Intervention/Treatment

Experimental: Nimotuzumab plus chemoradiotherapy

Drug: Nimotuzumab

Nimotuzumab:(200mg/w,weekly, 7-8 weeks, one week before radiotherapy) Radiotherapy: IMRT: Nasopharynx: GTV 66-78. 2Gy,CTV1 60-64Gy,CTV2 54-60Gy.30-34 times, 2.20-2.30Gy/time,once a day, 5 days/w, 6-7 weeks. Neck: lymph node positive, GTVn 60-70Gy, once a day, 5 days/w, 6-7weeks; lymph node negative, CTVn50-55Gy, once a day, 5 days/w, 6-7 weeks. CRT: Nasopharynx, 70-(76-80)Gy, 35-(38-40)times, 2Gy/time, once a day, 5 days/w, 6-8weeks. If disease residual when radiotherapy finished could increase the dose appropriate. Neck: lymph node positive, 64-70 Gy, 32-35 times, 2 Gy/time, once a day, 5 days/w, 6-7 weeks; lymph node negative, 50-56 Gy, 25-28 times,2 Gy/time, once a day, 5 days/w, 5-6weeks cisplatin Chemotherapy: Cisplatin (100 mg/m2,1 time/21d, 3 times，on days 2, 23, 44 during the radiotherapy)

Placebo Comparator: placebo plus chemoradiotherapy

Drug: placebo plus chemoradiotherapy

Placebo treatment:4 bottles/w,weekly, 7-8 weeks, one week before radiotherapy Radiotherapy: IMRT: Nasopharynx: GTV 66-78. 2Gy,CTV1 60-64Gy,CTV2 54-60Gy.30-34 times, 2.20-2.30Gy/time,once a day, 5 days/w, 6-7 weeks. Neck: lymph node positive, GTVn 60-70Gy, once a day, 5 days/w, 6-7weeks; lymph node negative, CTVn50-55Gy, once a day, 5 days/w, 6-7 weeks. CRT: Nasopharynx, 70-(76-80)Gy, 35-(38-40)times, 2Gy/time, once a day, 5 days/w, 6-8weeks. If disease residual when radiotherapy finished could increase the dose appropriate. Neck: lymph node positive, 64-70 Gy, 32-35 times, 2 Gy/time, once a day, 5 days/w, 6-7 weeks; lymph node negative, 50-56 Gy, 25-28 times,2 Gy/time, once a day, 5 days/w, 5-6weeks cisplatin Chemotherapy: Cisplatin (100 mg/m2,1 time/21d, 3 times，on days 2, 23, 44 during the radiotherapy)

Outcome Measures

Primary Outcome Measures

To determine the local-regional control rates of the disease in the advanced nasopharyngeal cancer patients subject to the treatment with Nimotuzumab in combination with chemoradiation [3 months after the Nimotuzumab treatment finished]
To determine the safety of the treatment with Nimotuzumab in combination with chemoradiation [within study period]

Secondary Outcome Measures

To determine the Disease-free survival、Tumor control probability、Distant recurrence rate in the patients subject to the treatment at years 1,2,3 [3 year]
To determine the Progression free suivival、Diease free survival、Overall survival in the patients subject to the treatment [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Joined the study voluntary and signed informed consent form
Age 18-70，both genders.
Nasopharyngeal cancer was confirmed by pathology.
Nasopharyngeal cancer 2008 Stages: Ⅲ/Ⅳa.
Primary lesions can measurable.
Karnofsky Performance Scale >70.
Life expectancy of more than 6 months.
Use of an effective contraceptive method for women when there is a risk of pregnancy during the study.
Haemoglobin≥100g/L ,WBC ≥4×109/L, platelet count≥100×109/L
Hepatic function:ALAT、ASAT< 1.5 x ULN, TBIL< 1.5 x ULN
Renal function: Creatinine < 1.5 x ULN

Exclusion Criteria:

Evidence of distant metastasis
Primary lesions or lymph node have been operated (except of operation for biopsy)
Previous radiotherapy
Received other anti EGFR monoclonal antibody treatment
Previous chemotherapy or immunization therapy
Other malignant tumor (except of Non-melanoma Skin Cancer or carcinoma in situ of cervix)
Participation in other interventional clinical trials within 1 month
Peripheral neuropathy is more than I stage
Pregnant or breast-feeding women and women who refused to take contraceptive method
History of serious allergic or allergy
History of Serious lung or heart disease
Refused or can't signed informed consent form
Drug abuse or alcohol addiction
Personality or psychiatric disease, and persons without capacity for civil conduct or persons with limited capacity for civil conduct

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fujian Medical University Union Hospital	Fuzhou	Fujian	China	350001
2	Fujian Provincial Cancer Hospital	Fuzhou	Fujian	China
3	Xiamen First Hospital	Xiamen	Fujian	China	361003
4	The Affiliated Cancer Hospital of Guangzhou Medical Hospital	Guangzhou	Guangdong	China	510095
5	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China
6	Affiliated Tumor Hospital of Guangxi Medical University	Xining	Guangxi	China	530021
7	The Fourth Hebei Province Hospital	Shijiazhuang	Hebei	China	050011
8	The Affiliated Cancer Hospital of Haerbin Medical University	Haerbin	Heilongjiang	China	150081
9	Henan Cancer Hospital	Zhengzhou	Henan	China	450008
10	Hubei Province Caner Hospital	Wuhan	Hubei	China	430079
11	Wuhan Union Hospital	Wuhan	Hubei	China
12	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110003
13	Liaoning Province Cancer Hospital	Shenyang	Liaoning	China	110042
14	Shandong Caner Hospital	Jinan	Shandong	China	250117
15	Sichuan Province Cancer Hospital	Chengdu	Sichuan	China
16	West China School of Medicine/West China Hospital of Sichuan University (WCSM/WCH)	Chengdu	Sichuan	China
17	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310022
18	Cancer Institute & Hospital.Chinese Academy of Medical Sciences	Beijing		China	100021
19	Peking Union Medical College Hospital	Beijing		China	100032
20	Beijing Cancer Hospital	Beijing		China	100142
21	The General Hospital of the People's Liberation Army	Beijing		China	100853
22	The Affiliated Renji Hosptial of ShanghaiJiao Tong University	Shanghai		China	200001
23	Fudan University Shanghai Cancer Center	ShangHai		China
24	Tianjin Cancer Hospital	Tianjin		China	300060