Nimotuzumab in Combination With Chemoradiation for Local Advanced Esophageal Squamous Cell Carcinoma

Sponsor

Biotech Pharmaceutical Co., Ltd. (Other)

Overall Status

Unknown status

CT.gov ID

NCT01232374

Collaborator

(none)

144

Enrollment

Locations

Arms

Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate Nimotuzumab in different indications. Nimotuzumab has been approved to treat squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal carcinoma in different countries. The clinical phase I study of the combination of Nimotuzumab administered concurrently with chemo-irradiation in patients with local advanced esophageal squamous cell carcinoma (LAFSCC) has shown the safety and the potential efficacy of Nimotuzumab. The concurrent trial is a clinical phase II trial designed to assess the efficacy of the combination of Nimotuzumab administered concurrently with chemo-radiotherapy in patients with LAFSCC, and to further investigate its side-effect and toxicity.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma	Drug: Nimotuzumab Drug: Placebo Drug: cisplatin Radiation: Radiotherapy	Phase 2

Detailed Description

The concurrent trial is a clinical phase II trial designed to assess the efficacy of the combination of Nimotuzumab administered concurrently with chemo-radiotherapy in patients with LAFSCC, and to further investigate its side-effect and toxicity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

A Clinical Study of Nimotuzumab in Combination With Concurrent Chemotherapy and Radiation for Patients With Local Advanced Esophageal Squamous Cell Carcinoma

Study Start Date :

Sep 1, 2010

Anticipated Primary Completion Date :

Oct 1, 2015

Anticipated Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nimotuzumab plus chemo-irradiation Nimotuzumab，chemotherapy(cisplatin )，radiotherapy	Drug: Nimotuzumab 200mg (4 bottles), once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13) Drug: cisplatin cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13). Radiation: Radiotherapy A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks. Placebo: 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)
Placebo Comparator: Placebo plus chemo-irradiation Placebo，chemotherapy(cisplatin)，radiotherapy	Drug: Placebo 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13) Other Names: Nimotuzumab, Placebo Drug: cisplatin cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13). Radiation: Radiotherapy A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks. Placebo: 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)

Arm

Intervention/Treatment

Experimental: Nimotuzumab plus chemo-irradiation

Nimotuzumab，chemotherapy(cisplatin )，radiotherapy

Drug: Nimotuzumab

200mg (4 bottles), once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)

Drug: cisplatin

cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13).

Radiation: Radiotherapy

A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks. Placebo: 4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)

Placebo Comparator: Placebo plus chemo-irradiation

Placebo，chemotherapy(cisplatin)，radiotherapy

Drug: Placebo

4 bottles placebo, once a week for 7 weeks during irradiation (week 1, week 2, week 3, week 4, week 5, week 6 and week 7). After irradiation 200mg (4 bottles), once every 4 weeks for 2 cycles (week 9 and week 13)

Other Names:

Nimotuzumab, Placebo

Drug: cisplatin

Radiation: Radiotherapy

Outcome Measures

Primary Outcome Measures

Response rate of Nimotuzumab combined with chemo-irradiation [2 months after radiotherapy]
1-yr overall survivals [1 year]
2-yr overall survival [2 year]
3-yr overall survival [3 years]

Secondary Outcome Measures

Local progression-free survival [3 years]
Disease progression-free survival [3 years]
Distant metastasis rate [3 years]
Number and grade of Participants with Adverse Events [6 months]
Quality of life [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Joined the study voluntarily and signed informed consent form;
Age 18-75
Both genders
Esophageal squamous cell carcinoma confirmed by pathology
Local advanced esophageal squamous cell carcinoma (T2N0M0-TxNxM1a, AJCC 2002)
No radiotherapy, chemotherapy or other treatments prior to enrollment
PS ECOG 0-2
Life expectancy of more than 3 months
Target lesions measurable
Hemoglobin（Hb）≥9 g/dL
WBC≥3x109/L, Neutrophils (ANC )≥1.5x109/L
platelet count (Pt) ≥100x 109/L
Hepatic function: ALAT and ASAT < 2.5 x ULN, TBIL<1.5 x ULN
Renal function: creatinine < 1.5 x ULN
No immuno-deficiency
Use of an effective contraceptive for adults to prevent pregnancy.

Exclusion Criteria:

Complete esophageal obstruction
Deep esophageal ulcer
Esophageal perforation
Haematemesis
After surgery, exploratory thoracotomy, radiotherapy, chemotherapy, or targeting therapy
Esophageal stent or tracheal stent placed
Other malignant tumors, except for skin basal cell carcinoma, or cervical carcinoma in situ, who survived with no evidence disease for over 3 years
Participation in other interventional clinical trials within 30 days
Pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives
Drug addiction
Alcoholism or AIDS
Uncontrolled seizures or psychiatric diseases, loss of control over their own behavior
History of serious allergic or allergy
Patients who are not suitable to participate in the trial according to researchers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chinese Academy of Medical Sciences Cancer Hospital	Beijing	Beijing	China	266000
2	Fujian Provincial Tumor Hospital	Fuzhou	Fujian	China	350000
3	Cancer Center of Sun Yat-sen	Guangzhou	Guangdong	China	510000
4	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450052
5	Huazhong University of Science and Technology, Union Hospital, Tongji Medical College	Wuhan	Hubei	China	430000
6	Cancer Hospital of Jiangsu Province	Nanjing	Jiangsu	China	210000
7	The First Affiliated Hospital of Soochow University,Suzhou First People's Hospital	Suzhou	Jiangsu	China	215006
8	Northern Jiangsu People's Hospital	Yangzhou	Jiangsu	China	225001
9	The first bethune hospital of Jilin university	Changchun	Jilin	China
10	Affiliated Hospital of Qingdao University Medical College	Qingdao	Shandong	China	266000
11	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200000
12	Shanghai Chest Hospital	Shanghai	Shanghai	China	201100
13	Shanghai First People's Hospital	Shanghai	Shanghai	China	201100
14	Fourth Military Medical University Xijing Hospital	Xian	Shanxi	China	710000
15	Tianjin Cancer Hospital	Tianjin	Tianjin	China	300000
16	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310000
17	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China	310003