Back to resultsStudy of Cetuximab in Combination With Chemotherapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Cetuximab
Cisplatin/Carboplatin
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, SCCHN
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of SCCHN
- Confirmed epidermal growth factor receptor (EGFR) expression in tumor tissue by immunohistochemistry (IHC)
- Expected survival is more than 6 months
- Presence of at least 1 bidimensionally measurable lesion either by computed tomography (CT) scan or magnetic resonance imaging (MRI)
- Recurrent and/or metastatic SCCHN not suitable for local therapy
- Greater than or equal to (>=) 20 years of age
- Karnofsky performance status (KPS) >= 70% at trial entry
- Neutrophils: >= 1500 per millimeter^3 (1,500/mm^3); platelet count >= 100,000/mm^3; and hemoglobin >= 9 gram per deciliter (g/dL)
- Total bilirubin less than or equal to (<=) 2 * upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 * ULN
- Creatinine clearance >60 milliliter per minute (mL/min).Calculated based on formulae such as the Cockroft-Gault formula for creatinine clearance
- Serum calcium within normal range (If serum albumin < 4.0 g/dL, the following adjusted serum calcium concentration should be within normality: Adjusted serum calcium concentration = actual serum calcium (milligram per deciliter [mg/dL]) - 0.8 * [actual serum albumin (g/dL) - 4]
- Effective contraception if risk of conception exists (applicable for both male and female subjects)
- Signed written informed consent
- Japanese (with Japanese citizenship)
Exclusion Criteria:
- Nasopharyngeal carcinoma
- 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
- Pregnancy (absence to be confirmed by serum/urine human chorionic gonadotropin [HCG] test) or breastfeeding
- Known hypersensitivity or allergic reaction against any of the components of the trial treatment including excipients
- Uncontrolled diabetes, malignant hypertension (defined as systolic blood pressure >= 180 millimeter of mercury [mmHg] and/or diastolic blood pressure >= 130 mmHg under resting conditions) or liver failure
- Pulmonary fibrosis, acute lung injury or interstitial pneumonia, or with previous medical history of these states
- Active infection, (infection requiring IV antibiotics, antibacterial, antifungal, or antiviral agent), including active tuberculosis, or known and declared human immunodeficiency virus (HIV)
- 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
- Current other squamous cell carcinoma (SCC) or previous other malignancy (excluding skin cancer except for melanoma and carcinoma in situ of the cervix or digestive tract) within the last 5 years
- Intake of any investigational medication within 30 days before trial entry
- Other concomitant anticancer therapies
- Documented or symptomatic brain or leptomeningeal metastasis
- Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent including known drug abuse
- Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or EGFR targeting therapy
- Legal incapacity or limited legal capacity
- Other protocol-defined exclusion criteria may apply
Sites / Locations
- Research Site
- National Cancer Center East Hospital
- Research Site
- Research Site
- Research Site
- Tokai University
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cetuximab + Cisplatin/Carboplatin + Fluorouracil (5-FU)
Arm Description
Outcomes
Primary Outcome Measures
Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria
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 in the sum of the products of diameters [SOPD] of index lesions compared to the baseline SOPD, with no evidence of PD) confirmed by a subsequent assessment no less than 28 days after criteria for response were first met based on modified WHO criteria as assessed by Independent Review Committee (IRC).
Secondary Outcome Measures
Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST as assessed by IRC. CR are those that persist on repeat imaging study at least 28 days after initial documentation of response. PR are those with greater than or equal to 30 percent decrease in the SOPD of index lesions compared to the baseline SOPD, with no evidence of PD.
Disease Control Rate
Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (>=50 percent decrease in sum of the products of diameters [SOPD] of index lesions compared to baseline SOPD, with no evidence of PD) confirmed by subsequent assessment no less than 28 days after criteria for response were first met) or stable disease [SD] (neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD) at least once no less than 42 days after first dose of trial treatment based on modified WHO criteria as assessed by IRC.
Duration of Response
Duration of response according to modified WHO criteria as assessed by IRC was defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death when death occurred within 60 days of the last tumor assessment or first administration of trial treatment (whichever was last).
Progression-Free Survival (PFS) Time
The PFS time according to modified WHO criteria as assessed by IRC was defined as duration from first administration of trial treatment until PD (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.
Overall Survival (OS) Time
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 to Treatment Failure
Time to treatment failure according to modified WHO criteria as assessed by IRC was defined as the time from first administration of trial treatment until the date of the first occurrence of one of the events defining treatment failure: PD assessed by the investigator, discontinuation of treatment due to PD, discontinuation of treatment due to an adverse event (AE), start of any new anticancer therapy, or withdrawal of consent or death within 60 days of the last tumor assessment or first administration of trial treatment.
Full Information
NCT ID
NCT00971932
First Posted
September 3, 2009
Last Updated
March 10, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00971932
Brief Title
Study of Cetuximab in Combination With Chemotherapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Official Title
Open-label, Single-arm, Multicenter, Phase II Study Investigating Cetuximab in Combination With Chemotherapy in the First-line Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) in Japanese Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
undefined (undefined)
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 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 of the head and neck (SCCHN) in Japanese 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, SCCHN
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab + Cisplatin/Carboplatin + Fluorouracil (5-FU)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cetuximab
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin/Carboplatin
Intervention Description
Subjects will receive 100 mg/m^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle. If subject developed non-hematological toxicities to cisplatin, carboplatin (area under curve 5 [AUC5]) will be administered as an IV infusion over 60 to 120 minutes on Day 1 of each 3-week treatment cycle.
Intervention Type
Drug
Intervention Name(s)
5-Fluorouracil
Intervention Description
Subjects will receive 1000 mg/m^2 per day 5-FU as a continuous IV infusion over 24 hours from day 1 to day 4 of each 3-week treatment cycle.
Primary Outcome Measure Information:
Title
Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria
Description
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 in the sum of the products of diameters [SOPD] of index lesions compared to the baseline SOPD, with no evidence of PD) confirmed by a subsequent assessment no less than 28 days after criteria for response were first met based on modified WHO criteria as assessed by Independent Review Committee (IRC).
Time Frame
Evaluations performed every 6 weeks until progressive disease (PD) reported between day of first participant treated, until cut-off date, 02 March 2011
Secondary Outcome Measure Information:
Title
Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Description
Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST as assessed by IRC. CR are those that persist on repeat imaging study at least 28 days after initial documentation of response. PR are those with greater than or equal to 30 percent decrease in the SOPD of index lesions compared to the baseline SOPD, with no evidence of PD.
Time Frame
Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011
Title
Disease Control Rate
Description
Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (>=50 percent decrease in sum of the products of diameters [SOPD] of index lesions compared to baseline SOPD, with no evidence of PD) confirmed by subsequent assessment no less than 28 days after criteria for response were first met) or stable disease [SD] (neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD) at least once no less than 42 days after first dose of trial treatment based on modified WHO criteria as assessed by IRC.
Time Frame
Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011
Title
Duration of Response
Description
Duration of response according to modified WHO criteria as assessed by IRC was defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death when death occurred within 60 days of the last tumor assessment or first administration of trial treatment (whichever was last).
Time Frame
Time from first assessment of CR or PR to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011
Title
Progression-Free Survival (PFS) Time
Description
The PFS time according to modified WHO criteria as assessed by IRC was defined as duration from first administration of trial treatment until PD (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
Time from first administration of trial treatment to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011
Title
Overall Survival (OS) Time
Description
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 first administration of trial treatment or last day known to be alive, reported between day of first participant treated, until cut-off date, 02 March 2011
Title
Time to Treatment Failure
Description
Time to treatment failure according to modified WHO criteria as assessed by IRC was defined as the time from first administration of trial treatment until the date of the first occurrence of one of the events defining treatment failure: PD assessed by the investigator, discontinuation of treatment due to PD, discontinuation of treatment due to an adverse event (AE), start of any new anticancer therapy, or withdrawal of consent or death within 60 days of the last tumor assessment or first administration of trial treatment.
Time Frame
Time from first administration of trial treatment to treatment failure or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed diagnosis of SCCHN
Confirmed epidermal growth factor receptor (EGFR) expression in tumor tissue by immunohistochemistry (IHC)
Expected survival is more than 6 months
Presence of at least 1 bidimensionally measurable lesion either by computed tomography (CT) scan or magnetic resonance imaging (MRI)
Recurrent and/or metastatic SCCHN not suitable for local therapy
Greater than or equal to (>=) 20 years of age
Karnofsky performance status (KPS) >= 70% at trial entry
Neutrophils: >= 1500 per millimeter^3 (1,500/mm^3); platelet count >= 100,000/mm^3; and hemoglobin >= 9 gram per deciliter (g/dL)
Total bilirubin less than or equal to (<=) 2 * upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 * ULN
Creatinine clearance >60 milliliter per minute (mL/min).Calculated based on formulae such as the Cockroft-Gault formula for creatinine clearance
Serum calcium within normal range (If serum albumin < 4.0 g/dL, the following adjusted serum calcium concentration should be within normality: Adjusted serum calcium concentration = actual serum calcium (milligram per deciliter [mg/dL]) - 0.8 * [actual serum albumin (g/dL) - 4]
Effective contraception if risk of conception exists (applicable for both male and female subjects)
Signed written informed consent
Japanese (with Japanese citizenship)
Exclusion Criteria:
Nasopharyngeal carcinoma
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
Pregnancy (absence to be confirmed by serum/urine human chorionic gonadotropin [HCG] test) or breastfeeding
Known hypersensitivity or allergic reaction against any of the components of the trial treatment including excipients
Uncontrolled diabetes, malignant hypertension (defined as systolic blood pressure >= 180 millimeter of mercury [mmHg] and/or diastolic blood pressure >= 130 mmHg under resting conditions) or liver failure
Pulmonary fibrosis, acute lung injury or interstitial pneumonia, or with previous medical history of these states
Active infection, (infection requiring IV antibiotics, antibacterial, antifungal, or antiviral agent), including active tuberculosis, or known and declared human immunodeficiency virus (HIV)
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
Current other squamous cell carcinoma (SCC) or previous other malignancy (excluding skin cancer except for melanoma and carcinoma in situ of the cervix or digestive tract) within the last 5 years
Intake of any investigational medication within 30 days before trial entry
Other concomitant anticancer therapies
Documented or symptomatic brain or leptomeningeal metastasis
Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent including known drug abuse
Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or EGFR targeting therapy
Legal incapacity or limited legal capacity
Other protocol-defined exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark P. Smith, MD
Organizational Affiliation
Merck Serono Co., Ltd., Japan
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Aichi
Country
Japan
Facility Name
National Cancer Center East Hospital
City
Chiba
Country
Japan
Facility Name
Research Site
City
Ehime
Country
Japan
Facility Name
Research Site
City
Hokkaido
Country
Japan
Facility Name
Research Site
City
Kanagawa
Country
Japan
Facility Name
Tokai University
City
Kanagawa
Country
Japan
Facility Name
Research Site
City
Osaka
Country
Japan
Facility Name
Research Site
City
Shizuoka
Country
Japan
Facility Name
Research Site
City
Tochigi
Country
Japan
Facility Name
Research Site
City
Tokyo
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
23479384
Citation
Yoshino T, Hasegawa Y, Takahashi S, Monden N, Homma A, Okami K, Onozawa Y, Fujii M, Taguchi T, de Blas B, Beier F, Tahara M. Platinum-based chemotherapy plus cetuximab for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: results of a phase II trial. Jpn J Clin Oncol. 2013 May;43(5):524-31. doi: 10.1093/jjco/hyt034. Epub 2013 Mar 10.
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Study of Cetuximab in Combination With Chemotherapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
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