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

Sponsor

The Second People's Hospital of Sichuan (Other)

Overall Status

Unknown status

CT.gov ID

NCT01516996

Collaborator

Biotech Pharmaceutical Co., Ltd. (Other)

Enrollment

Locations

Arms

Duration (Months)

6.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Oropharyngeal Cancer Hypopharyngeal Cancer	Drug: docetaxel and cisplatin Radiation: IMRT Biological: Nimotuzumab	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2012

Anticipated Primary Completion Date :

Sep 1, 2013

Anticipated Study Completion Date :

Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Neoadjuvant and CCRT	Drug: docetaxel and cisplatin 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 Radiation: IMRT 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 Other Names: CCRT
Experimental: Neoadjuvant and CCRT and Nimotuzumab	Drug: docetaxel and cisplatin 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 Radiation: IMRT 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 Other Names: CCRT Biological: Nimotuzumab Nimotuzumab was administered 200 mg IV over 1 hour on day 1,once a week, for 13~14 weeks

Arm

Intervention/Treatment

Active Comparator: Neoadjuvant and CCRT

Drug: docetaxel and cisplatin

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

Radiation: IMRT

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

Other Names:

CCRT

Experimental: Neoadjuvant and CCRT and Nimotuzumab

Drug: docetaxel and cisplatin

Radiation: IMRT

Other Names:

CCRT

Biological: Nimotuzumab

Nimotuzumab was administered 200 mg IV over 1 hour on day 1,once a week, for 13~14 weeks

Outcome Measures

Primary Outcome Measures

Objective response rate [3 months after all the treatment ending]
Objective Response Rate: Complete response (CR)+ partial response (PR) rates base on RECIST evaluation system.
The Number of Participants with Adverse Events [Participants will be followed during the treatment and 3 months after all the treatment ending ,an expected average of 26 weeks]
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.

Secondary Outcome Measures

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. [Participants will be followed every year for the duration of 5 years]
To evaluate each year until 5 years later
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gansu Province Medical Science Institute	Lanzhou	Gansu	China	730050
2	Guangxi Tumor Hospital	Nanning	Guangxi	China	530021
3	GuiZhou Cancer Hospital	Guiyang	Guizhou	China	550004
4	Neimenggu Tumor Hospital	Baotou	Neimenggu	China	014030
5	The Tumor Affiliated Hospital of Ningxia Medical University General Hospita	Yinchuan	Ningxia	China	750004
6	Qinghai Five Hospital	Xining	Qinghai	China
7	Xijing Hospital	Xi-an	Shanxi	China	710032
8	ShanXi Cancer Hospital	Xian	Shanxi	China	710061
9	The Second People's Hospital of Sichuan	Chengdu	Sichuan	China	610041
10	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
11	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University	Chongqing	Sichuan	China	400042
12	Xinjiang tumor hospital, The Third Affiliated Hospital of Xinjiang Medical University	Wulumuqi	Xinjiang	China	830000
13	Yunnan Tumor Hospital, The Third Affiliated Hospital of KUNMING Medical University	Kunming	Yunnan	China	652100