Study of Cetuximab in Nasopharyngeal Carcinoma (NPC) With Chemoradiotherapy (ENCORE)

• ClinicalTrials.gov Identifier: NCT00700440
• Recruitment Status: Completed
• First Posted: June 18, 2008
• Results First Posted: March 26, 2010
• Last Update Posted: March 26, 2010
• Sponsor: Sun Yat-sen University
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Sichuan Cancer Hospital and Research Institute; Fujian Cancer Hospital; Fudan University; Cancer Hospital of Guizhou Province; First Affiliated Hospital of Guangxi Medical University; Central South University
• Information provided by: Sun Yat-sen University

Study Description

Brief Summary:

This is an open, multicenter phase Ⅱ clinical trial on cetuximab (C225) combined with IMRT + concurrent chemotherapy of cisplatin in locoregionally advanced nasopharyngeal carcinoma.

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma	Drug: C225 (cetuximab)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Cetuximab Combined With Intensity Modulated Radiotherapy (IMRT) and Concurrent Chemotherapy of Cisplatin in Nasopharyngeal Carcinoma
• Study Start Date: July 2008
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cetuximab; 400mg/m^2 intravenous infusion one week before radiotherapy, then 250mg/m^2 intravenous infusion weekly during radiotherapy	Drug: C225 (cetuximab); one week before and then weekly during radiotherapy; Other Name: Erbitux

Outcome Measures

Primary Outcome Measures :

1. 3 Month Loco-regional Control After Cetuximab With Concurrent Chemoradiotherapy [ Time Frame: 3 months ]

   The response status (Complete Response + Partial Response) was evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Complete response was defined as disappearance of all target lesions, and Partial response was defined as at least a 30% reduction in the sum of the longest diameter of target lesions, taking as reference the baseline study.

   Adverse events of this combined modality treatment were graded according to CTCAE (Common Terminology Criteria for Adverse Events) v3.0 criteria.

Secondary Outcome Measures :

1. 1,3,5 Year Loco-regional Control Rate, 1 Year Progression-free Survival and Metastasis-free Survival, 3 and 5 Year Overall Survival [ Time Frame: 5 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 69 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Informed consent form signed prior to study entry
• Age between 18-69 years old
• Pathology approved to be nasopharyngeal carcinoma (types WHO Ⅱ-Ⅲ)
• Stage Ⅲ, Ⅳa, Ⅳb according to UICC (International Union Against Cancer) 2002 6th edition criteria
• Primary tumor measurable
• KPS score ≥80
• Expected life span ≥6 months
• Adequate bone marrow function: White Blood Cell≥4×109/L，Hemoglobin≥100g/L，Platelet≥100×109/L
• Adequate liver function: ALAT/ASAT<1.5 × upper limit of normal (ULN), bilirubin <1.5×ULN
• Adequate renal function: Creatinine Clearance < 1.5×ULN

Exclusion Criteria:

• Evidence of distant metastatic disease
• Surgical procedure of the primary tumor or lymph nodes (except diagnostic biopsy)
• Previous radiotherapy for the primary tumor or lymph nodes
• Previous exposure to epidermal growth factor-targeted therapy
• Prior chemotherapy or immunotherapy for the primary tumor
• Other previous malignancy within 5 years, except non-melanoma skin cancer or pre-invasive carcinoma of the cervix
• Any investigational agent prior to the 1st study medication
• Participation in another clinical study within the 30 days prior to Inclusion in this study.
• Peripheral neuropathy > grade 1
• Known grade 3 or 4 allergic reaction to any of the study treatment
• History of severe pulmonary or cardiac disease
• Creatinine Clearance < 30ml/min
• Know drug abuse / alcohol abuse
• Legal incapacity or limited legal capacity
• Active systemic infection
• Medical or psychiatric illness, which in the investigators' opinions, would not permit the subject to complete or fully and completely understand the risks and potential complications of the study
• Concurrent chronic systemic immune therapy or hormone therapy not indicated in the study protocol
• Pregnancy (confirmed by serum or urine β-HCG) or lactation period
• Severe intercurrent illness, e.g. uncontrolled hypertension, cardiac failure

Contacts and Locations

Locations

China, Guangdong

Cancer Center, Sun Yat-sen University

Guangzhou, Guangdong, China, 510080

Sponsors and Collaborators

Sun Yat-sen University

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Sichuan Cancer Hospital and Research Institute

Fujian Cancer Hospital

Fudan University

Cancer Hospital of Guizhou Province

First Affiliated Hospital of Guangxi Medical University

Central South University

Investigators

• Principal Investigator: Tai-xiang Lu, M.D.; Departments of Radiation Oncology, Cancer Center, Sun Yat-sen University
• Principal Investigator: Tong-yu Lin, M.D., PhD; Departments of Chemotherapy, Cancer Center, Sun Yat-sen University

More Information

Additional Information:

Home Page of Chinese Anti-Cancer Association 

Publications:

Sung FL, Poon TC, Hui EP, Ma BB, Liong E, To KF, Huang DP, Chan AT. Antitumor effect and enhancement of cytotoxic drug activity by cetuximab in nasopharyngeal carcinoma cells. In Vivo. 2005 Jan-Feb;19(1):237-45.

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78.

Kiss R, Salmon I, Pauwels O, Gras S, Danguy A, Etievant C, Pasteels JL, Martinez J. In vitro influence of gastrin, oestradiol and gonadotropin-releasing hormone on HCT-15 and LoVo human colorectal neoplastic cell proliferation. Eur J Cancer. 1991;27(10):1268-74.

Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005 Dec 1;23(34):8646-54. Erratum in: J Clin Oncol. 2006 Feb 1;24(4):724.

Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. Erratum in: J Clin Oncol. 2007 Aug 20;25(24):3790.

• Responsible Party: Departments of Radiation Oncology, Cancer Center, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT00700440
• Other Study ID Numbers: EMR62202-770; PPRA-RTOG 0001
• First Posted: June 18, 2008
• Results First Posted: March 26, 2010
• Last Update Posted: March 26, 2010
• Last Verified: February 2009

Keywords provided by Sun Yat-sen University:

Radiotherapy; chemotherapy; Drug Targeting; loco-regionally advanced nasopharyngeal carcinoma; Safety.; efficacy

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Cetuximab; Antineoplastic Agents, Immunological; Antineoplastic Agents