Back to resultsA 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 (CHANGE)
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cetuximab
Cisplatin
5-Fluorouracil
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Recurrent and/or metastatic squamous cell carcinoma of the head and neck, 1st-line, Cetuximab, Chemotherapy, EMR 62241 -055, Merck KGaA, Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)
Eligibility Criteria
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
Sites / Locations
- Cancer Institute & Hospital, Chinese Academy of Medical Sciences
- Jilin Cancer Hospital
- The Xiangya 2nd Hospital of Central South University
- Fuijan Provincial Tumor Hospital
- Nanfang Hospital of Nanfang Medical University
- Sun Yat-Sen Univesity Cancer Center
- Zhejiang Provincial Tumor Hospital
- Jiangsu Cancer Hospital
- Tumor Hospital of Guangxi Zhuang Autonomous Region / The Tumor Affiliated Hospital of Guangxi Medical University
- Eye & ENT Hospital of Fundan University
- Fundan University Shanghai Cancer Center
- Tongji Hospital of Tongji Medical College of Huazhong University of Science & Technology
- Xijing Hospital, the Fourth Military Medical University
- Clinical Trial Center of Medical Research Institute, Pusan National University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cetuximab + Cisplatin + 5-Fluorouracil (5-FU)
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01177956
First Posted
June 2, 2010
Last Updated
August 25, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT01177956
Brief Title
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
Acronym
CHANGE
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
Keywords
Recurrent and/or metastatic squamous cell carcinoma of the head and neck, 1st-line, Cetuximab, Chemotherapy, EMR 62241 -055, Merck KGaA, Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
73 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab + Cisplatin + 5-Fluorouracil (5-FU)
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Subjects will receive 75 mg/m^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Best Overall Response (BOR) Until Cut-off Date 25 January 2011
Description
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.
Time Frame
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
Title
Best Overall Response (BOR) Until Cut-off Date 15 November 2012
Description
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.
Time Frame
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
Secondary Outcome Measure Information:
Title
Overall Survival (OS) Time Until Cut-off Date 15 November 2012
Description
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 Frame
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
Title
Progression-free Survival (PFS) Time Until Cut-off Date 25 January 2011
Description
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.
Time Frame
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
Title
Progression-free Survival (PFS) Time Until Cut-off Date 15 November 2012
Description
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.
Time Frame
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
Title
Time to Progression (TTP) Until Cut-off Date 25 January 2011
Description
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.
Time Frame
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
Title
Time to Progression (TTP) Until Cut-off Date 15 November 2012
Description
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.
Time Frame
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
Title
Duration of Response Until Cut-off Date 25 January 2011
Description
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.
Time Frame
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
Title
Duration of Response Until Cut-off Date 15 November 2012
Description
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.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Cancer Institute & Hospital, Chinese Academy of Medical Sciences
City
Beijing
Country
China
Facility Name
Jilin Cancer Hospital
City
Changchun
Country
China
Facility Name
The Xiangya 2nd Hospital of Central South University
City
Changsha City
Country
China
Facility Name
Fuijan Provincial Tumor Hospital
City
Fuijian
Country
China
Facility Name
Nanfang Hospital of Nanfang Medical University
City
Guangzhou
Country
China
Facility Name
Sun Yat-Sen Univesity Cancer Center
City
Guangzhou
Country
China
Facility Name
Zhejiang Provincial Tumor Hospital
City
Hangzhou
Country
China
Facility Name
Jiangsu Cancer Hospital
City
Jiangsu, Nanjing
Country
China
Facility Name
Tumor Hospital of Guangxi Zhuang Autonomous Region / The Tumor Affiliated Hospital of Guangxi Medical University
City
Nanning City
Country
China
Facility Name
Eye & ENT Hospital of Fundan University
City
Shanghai
Country
China
Facility Name
Fundan University Shanghai Cancer Center
City
Shanghai
Country
China
Facility Name
Tongji Hospital of Tongji Medical College of Huazhong University of Science & Technology
City
Wuhan City
Country
China
Facility Name
Xijing Hospital, the Fourth Military Medical University
City
Xi'an
Country
China
Facility Name
Clinical Trial Center of Medical Research Institute, Pusan National University Hospital
City
Busan
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
24710768
Citation
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, Lupfert C, Cai J, Shi Y. Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial. Head Neck. 2015 Aug;37(8):1081-7. doi: 10.1002/hed.23707. Epub 2014 Sep 17.
Results Reference
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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
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