Squamous Cell Carcinoma of the Head and Neck
Conditions
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)
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.
Interventions
BIOLOGICALCetuximab
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.
DRUGCisplatin
Subjects will receive 75 mg/m\^2 cisplatin as an IV infusion over 60 minutes on day 1 of each 3-week treatment cycle.
DRUG5-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.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) Until Cut-off Date 25 January 2011 | 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 | 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Time Until Cut-off Date 15 November 2012 | 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 | 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 | 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 | 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. |
| Overall Survival (OS) Time Until Cut-off Date 15 November 2012 | 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 | 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. |
| Duration of Response Until Cut-off Date 25 January 2011 | 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 | 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 | 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 | 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 to Progression (TTP) Until Cut-off Date 15 November 2012 | 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 | 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. |
| Progression-free Survival (PFS) Time Until Cut-off Date 25 January 2011 | 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 | 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. |
Countries
China, South Korea
Participant flow
Recruitment details
First/last participant (informed consent): December 2009/September 2010. Clinical data cut-off: 25 January 2011, Study completion date: November 2012
Pre-assignment details
A total of 73 participants were enrolled, out of which 5 participants were screen failure and 68 participants received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab + Cisplatin + 5-FU Participants were administered an initial dose of cetuximab 400 milligram per square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes followed by subsequent weekly doses of 250 mg/m\^2 IV infusion over 60 minutes along with background chemotherapy consisting of cisplatin 75 mg/m\^2 IV infusion over 60 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 750 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 5 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity. | 68 |
| Total | 68 |
Baseline characteristics
| Characteristic | Cetuximab + Cisplatin + 5-FU |
|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 9.5 |
| Age, Customized <65 years | 55 participants |
| Age, Customized >=65 years | 13 participants |
| Race/Ethnicity, Customized Asian (Chinese) | 63 participants |
| Race/Ethnicity, Customized Asian (Korean) | 5 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 67 / 68 | 0 / 32 |
| serious Total, serious adverse events | 13 / 68 | 0 / 32 |
Outcome results
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.
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
Population: ITT population included all participants who received at least one dose of the investigational medicinal product (IMP) cetuximab or chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Best Overall Response (BOR) Until Cut-off Date 15 November 2012 | 55.9 percentage of participants |
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.
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
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Best Overall Response (BOR) Until Cut-off Date 25 January 2011 | 54.4 percentage of participants |
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.
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
Population: Subgroup of participants from the study population having best confirmed response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Duration of Response Until Cut-off Date 15 November 2012 | 6.1 months |
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.
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
Population: Subgroup of participants from the study population having best confirmed response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Duration of Response Until Cut-off Date 25 January 2011 | 5.7 months |
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 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
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Overall Survival (OS) Time Until Cut-off Date 15 November 2012 | 12.6 months |
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.
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
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Progression-free Survival (PFS) Time Until Cut-off Date 15 November 2012 | 6.6 months |
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.
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
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Progression-free Survival (PFS) Time Until Cut-off Date 25 January 2011 | 6.2 months |
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.
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
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Time to Progression (TTP) Until Cut-off Date 15 November 2012 | 7.0 months |
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.
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
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin + 5-FU | Time to Progression (TTP) Until Cut-off Date 25 January 2011 | 6.8 months |