Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

— CHANCE  

Official title:

Open-label, Single-arm, Multicenter, Phase III Trial to Assess the Antitumor Activity and Safety of Cetuximab When Given in Combination With Radiotherapy for the Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01012258
• Other study ID #: EMR62241-054
• Status: Completed
• Phase: Phase 3
• First received: November 10, 2009
• Last updated: June 11, 2015
• Start date: February 2009
• Est. completion date: May 2014

Study information

• Verified date: June 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary objective: to assess the antitumor activity and safety profile of cetuximab when given in combination with radiotherapy (RT) for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in Chinese subjects.

Secondary objective: to assess the pharmacokinetic (PK) profile and immunogenicity of cetuximab in Chinese subjects.

Further objective: to identify for cetuximab potential predictive biomarkers of response and safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 2014
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Inpatient greater than or equal to (>=) 18 years of age

• Pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx or larynx

• Stage III or IV disease with an expected survival of at least 12 months

• Medically suitable to withstand a course of concomitant boost RT

• Presence of at least 1 bi-dimensionally measurable lesion identified either by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified World Health Organization (WHO) criteria

• Karnofsky Performance Status (KPS) >=80 at trial entry

• Neutrophils >=1.5*10^9/Liter (L), platelet count >= 100*10^9/L, hemoglobin >= 90 gram/liter (g/L)

• Total bilirubin less than or equal to (<=) 2*upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3*ULN

• Serum creatinine <=133 micromole/liter (mcmol/L)

• Serum calcium within normal range

• Effective contraception if procreative potential exists (applicable to both male and female subjects)

• Chinese with Chinese citizenship

• Signed written informed consent

Exclusion Criteria:

• Evidence of distant metastatic disease

• Squamous cell carcinoma arising in the nasopharynx or oral cavity

• Receipt of prior systemic chemotherapy within the last 3 years

• Previous surgery for the tumor under study other than biopsy

• Receipt of prior RT to the head and neck

• Currently receiving RT as part of a postoperative regimen following primary surgical resection

• Planned neck dissection after trial RT

• Active infection (infection requiring IV antibiotics), including active tuberculosis, or known and declared human immunodeficiency virus (HIV)

• Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder, interstitial pneumonia, cardiac failure or liver failure

• Uncontrolled hypertension defined as systolic blood pressure >=180 millimeter of mercury (mmHg) and/or diastolic blood pressure >=130 mmHg under resting conditions

• Pregnancy (absence to be confirmed by serum beta human chorionic gonadotrophin [beta-HCG] test) or breastfeeding

• Concomitant chronic systemic immune therapy or hormonal therapy as cancer therapy

• Other concomitant anticancer therapies

• Documented or symptomatic brain or leptomeningeal metastasis

• Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency

• Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or epidermal growth factor receptor (EGFR) targeting therapy

• Evidence of previous other malignancy within the last 5 years

• Intake of any investigational medication within 30 days before trial entry

• Other protocol-defined exclusion criteria may apply

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Biological:
• Cetuximab + concomitant boost radiotherapy
Cetuximab 400 milligram/square meter (mg/m^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially Once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by Twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses are separated by at least a 6-hour interval

Locations

Country	Name	City	State
China	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	Beijing
China	Xiangya Hospital of Central South University	Changsha, Hunan
China	Fujian Provincial Tumor Hospital	Fuzhou	Fujian
China	Sun Yat-sen University Cancer Center	Guangzhou
China	Zhejiang Provincial Cancer Hospital	Hangzhou
China	Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan, Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan, Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response (BOR)	Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD.	Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit	No
Secondary	Progression-Free Survival (PFS)	Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later).	Baseline up to disease progression or withdrawal or 12 weeks after the last radiotherapy of the last participant	No