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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hypopharyngeal Cancer; Oropharyngeal Cancer
• Intervention / Treatment: Drug: docetaxel and cisplatin; Radiation: IMRT; Biological: Nimotuzumab

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730050
      • Active, not recruiting
      • Gansu Province Medical Science Institute
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Active, not recruiting
      • Guangxi Tumor Hospital
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • Active, not recruiting
      • Guizhou Cancer Hospital
  • Neimenggu
    • Baotou, Neimenggu, China, 014030
      • Active, not recruiting
      • Neimenggu Tumor Hospital
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • Active, not recruiting
      • The Tumor Affiliated Hospital of Ningxia Medical University General Hospita
  • Qinghai
    • Xining, Qinghai, China
      • Active, not recruiting
      • Qinghai Five Hospital
  • Shanxi
    • Xi-an, Shanxi, China, 710032
      • Active, not recruiting
      • Xijing Hospital
    • Xian, Shanxi, China, 710061
      • Active, not recruiting
      • Shanxi Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Active, not recruiting
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • The Second People's Hospital of Sichuan
      • Contact: Peng Xu, M.D.; Phone Number: 15828312322; Email: xupeng4618@163.com
    • Chongqing, Sichuan, China, 400042
      • Active, not recruiting
      • Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
  • Xinjiang
    • Wulumuqi, Xinjiang, China, 830000
      • Active, not recruiting
      • Xinjiang tumor hospital, The Third Affiliated Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China, 652100
      • Active, not recruiting
      • Yunnan Tumor Hospital, The Third Affiliated Hospital of KUNMING Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	To evaluate each year until 5 years later	Participants will be followed every year for the duration of 5 years
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

Collaborators and Investigators

• Sponsor: The Second People's Hospital of Sichuan
• Collaborators: Biotech Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yi J Lang, M.D., Radiotherapy Department

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: January 11, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (Estimate): January 25, 2012

Study Record Updates

• Last Update Posted (Estimate): March 20, 2012
• Last Update Submitted That Met QC Criteria: March 18, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Randomized; Neoadjuvant; Multicenter; Nimotuzumab; Hypopharynx cancer; Concurrent Chemoradiotherapy,CCRT; Locoregionally Advanced Oropharynx
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms; Hypopharyngeal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Nimotuzumab
• Other Study ID Numbers: BT-IST-SCCHN-036