A Trial to Determine the Safety and Anti-tumor Activity Profile of the Combination of Cetuximab and Concomitant Cisplatin Plus 5-Fluorouracil (5-FU) in Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma in Head and Neck

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

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Official title:

Open-label, Single-arm, Multicenter, Phase III Trial to Assess the Antitumor Activity and Safety Profile of Cetuximab When Given in Combination With Chemotherapy for the First-line Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck in Asian Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01177956
• Other study ID #: EMR62241_055
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2010
• Last updated: August 25, 2014
• Start date: December 2009
• Est. completion date: November 2012

Study information

• Verified date: August 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of HealthChina: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this trial is to assess the antitumor activity and safety profile of cetuximab when given in combination with cisplatin + 5-Fluorouracil (5-FU) for the first-line treatment of recurrent and/or metastatic Squamous Cell Carcinoma in Head and Neck (SCCHN) in Asian subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: November 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written informed consent

• Inpatient

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

• Histologically or cytologically confirmed diagnosis of SCCHN

• Recurrent and/or metastatic SCCHN not suitable for local therapy

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

• Karnofsky performance status (KPS) >= 80 percent at trial entry

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

• Serum calcium within normal range

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

Exclusion Criteria:

• Prior systemic chemotherapy, except if given as part of a multimodal treatment which was completed more than 6 months prior to trial entry

• Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry

• Nasopharyngeal carcinoma

• 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

• Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent

• Known drug abuse (with the exception of alcohol abuse)

• Known hypersensitivity or allergic reaction against any of the components of the trial treatment

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

• Previous or current other squamous cell carcinoma (SCC)

• Evidence of previous other malignancy within the last 5 years

• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such

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

• Legal incapacity or limited legal capacity

• Other significant disease that in the Investigator's opinion would exclude the subject from the trial

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
The initial dose of cetuximab will be 400 milligram per square meter (mg/m^2) as an intravenous (IV) infusion over 120 minutes. Subsequent weekly doses will be 250 mg/m^2 as an IV infusion over 60 minutes. Chemotherapy will be continued for up to a maximum of six 3-week cycles in the absence of progressive disease (PD) or unacceptable toxicity. All subjects will receive cetuximab treatment until the occurrence of PD or unacceptable toxicity to cetuximab.

Drug:
• Cisplatin
Subjects will receive 75 mg/m^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle.
• 5-Fluorouracil
Subjects will receive 750 mg/m^2 per day 5-FU as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle.

Locations

Country	Name	City	State
China	Cancer Institute & Hospital, Chinese Academy of Medical Sciences	Beijing
China	Jilin Cancer Hospital	Changchun
China	The Xiangya 2nd Hospital of Central South University	Changsha City
China	Fuijan Provincial Tumor Hospital	Fuijian
China	Nanfang Hospital of Nanfang Medical University	Guangzhou
China	Sun Yat-Sen Univesity Cancer Center	Guangzhou
China	Zhejiang Provincial Tumor Hospital	Hangzhou
China	Jiangsu Cancer Hospital	Jiangsu, Nanjing
China	Tumor Hospital of Guangxi Zhuang Autonomous Region / The Tumor Affiliated Hospital of Guangxi Medical University	Nanning City
China	Eye & ENT Hospital of Fundan University	Shanghai
China	Fundan University Shanghai Cancer Center	Shanghai
China	Tongji Hospital of Tongji Medical College of Huazhong University of Science & Technology	Wuhan City
China	Xijing Hospital, the Fourth Military Medical University	Xi'an
Korea, Republic of	Clinical Trial Center of Medical Research Institute, Pusan National University Hospital	Busan

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

China,  Korea, Republic of, 

References & Publications (1)

Guo Y, Shi M, Yang A, Feng J, Zhu X, Choi YJ, Hu G, Pan J, Hu C, Luo R, Zhang Y, Zhou L, Cheng Y, Lüpfert C, Cai J, Shi Y. Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response (BOR) Until Cut-off Date 25 January 2011	BOR: Percentage of participants experiencing a Complete Response (CR) (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (PR) (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified World Health Organization [WHO] criteria), divided by the number of participants belonging to intention to treat (ITT) or safety population.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011	No
Primary	Best Overall Response (BOR) Until Cut-off Date 15 November 2012	BOR: Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (greater than or equal to 50 percent decrease of sum of product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions confirmed by a subsequent assessment no less than 28 days after criteria for response were first met) (based on modified WHO criteria), divided by the number of participants belonging to ITT or safety population.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012	No
Secondary	Overall Survival (OS) Time Until Cut-off Date 15 November 2012	The OS time was defined as the time from first administration of trial treatment to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.	Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012	No
Secondary	Progression-free Survival (PFS) Time Until Cut-off Date 25 January 2011	Duration from first administration of trial treatment until progression (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011	No
Secondary	Progression-free Survival (PFS) Time Until Cut-off Date 15 November 2012	Duration from first administration of trial treatment until progression (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012	No
Secondary	Time to Progression (TTP) Until Cut-off Date 25 January 2011	Time from first administration of trial treatment to disease progression (radiological or clinical, if radiological progression is not available). Participants without event are censored on the date of last tumor assessment.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011	No
Secondary	Time to Progression (TTP) Until Cut-off Date 15 November 2012	Time from first administration of trial treatment to disease progression (radiological or clinical, if radiological progression is not available). Participants without event are censored on the date of last tumor assessment.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012	No
Secondary	Duration of Response Until Cut-off Date 25 January 2011	Time from first assessment of CR or PR to disease progression or death (within 60 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 25 January 2011	No
Secondary	Duration of Response Until Cut-off Date 15 November 2012	Time from first assessment of CR or PR to disease progression or death (within 60 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria.	Evaluations were performed every 6 weeks until progression, reported between day of first participant randomized, 25 December 2009, until cut-off date 15 November 2012	No