Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
Recurrent and/or metastatic, SCCHN
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.
Interventions
DRUGCetuximab
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.
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.
DRUG5-Fluorouracil
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.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of SCCHN 2. Confirmed epidermal growth factor receptor (EGFR) expression in tumor tissue by immunohistochemistry (IHC) 3. Expected survival is more than 6 months 4. Presence of at least 1 bidimensionally measurable lesion either by computed tomography (CT) scan or magnetic resonance imaging (MRI) 5. Recurrent and/or metastatic SCCHN not suitable for local therapy 6. Greater than or equal to (\>=) 20 years of age 7. Karnofsky performance status (KPS) \>= 70% at trial entry 8. Neutrophils: \>= 1500 per millimeter\^3 (1,500/mm\^3); platelet count \>= 100,000/mm\^3; and hemoglobin \>= 9 gram per deciliter (g/dL) 9. Total bilirubin less than or equal to (\<=) 2 \* upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<= 3 \* ULN 10. Creatinine clearance \>60 milliliter per minute (mL/min).Calculated based on formulae such as the Cockroft-Gault formula for creatinine clearance 11. 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 \* \[actual serum albumin (g/dL) - 4\] 12. Effective contraception if risk of conception exists (applicable for both male and female subjects) 13. Signed written informed consent 14. Japanese (with Japanese citizenship)
Exclusion criteria
1. Nasopharyngeal carcinoma 2. Prior systemic chemotherapy, except if given as part of a multimodal treatment, which was completed more than 6 months prior to trial entry 3. Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry 4. Pregnancy (absence to be confirmed by serum/urine human chorionic gonadotropin \[HCG\] test) or breastfeeding 5. Known hypersensitivity or allergic reaction against any of the components of the trial treatment including excipients 6. 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 7. Pulmonary fibrosis, acute lung injury or interstitial pneumonia, or with previous medical history of these states 8. Active infection, (infection requiring IV antibiotics, antibacterial, antifungal, or antiviral agent), including active tuberculosis, or known and declared human immunodeficiency virus (HIV) 9. 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 10. 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 11. Intake of any investigational medication within 30 days before trial entry 12. Other concomitant anticancer therapies 13. Documented or symptomatic brain or leptomeningeal metastasis 14. Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent including known drug abuse 15. Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or EGFR targeting therapy 16. Legal incapacity or limited legal capacity 17. Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria | Evaluations performed every 6 weeks until progressive disease (PD) reported between day of first participant treated, until cut-off date, 02 March 2011 | 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
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011 | 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 | 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 | 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). |
| Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011 | 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. |
| Overall Survival (OS) Time | 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 | 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 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 | 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. |
| Progression-Free Survival (PFS) Time | 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 | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (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 100 mg/m\^2 IV infusion over 60 to 120 minutes on day 1 of each 3-week treatment cycle and 5-fluorouracil (5-FU) 1000 mg/m\^2 per day as a continuous IV infusion over 24 hours from day 1 to day 4 of each 3-week treatment cycle, for up to 6 cycles in the absence of progressive disease (PD) or unacceptable toxicity. If participant developed non-hematological toxicities to cisplatin, carboplatin (area under curve 5 \[AUC5\]) was administered as IV infusion over 60 to 120 minutes on Day 1 of each 3-week treatment cycle. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Investigator's decision | 2 |
| Overall Study | Ongoing | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) |
|---|---|
| Age, Continuous | 57.20 years STANDARD_DEVIATION 11.42 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 12 / 33 |
Outcome results
Primary
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).
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
Population: Intention-to-treat (ITT) population included all participants who received at least one dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria | 36.4 percentage of participants |
Secondary
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.
Time frame: Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011
Population: ITT population included all participants who received at least one dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | 45.5 percentage of participants |
Secondary
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.
Time frame: Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011
Population: ITT population included all participants who received at least one dose of the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Disease Control Rate | 87.9 percentage of participants |
Secondary
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).
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
Population: Subgroup of participants from the study population with a best overall response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Duration of Response | 2.8 months |
Secondary
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 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
Population: ITT population included all participants who received at least one dose of the study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Overall Survival (OS) Time | 12.8 months |
Secondary
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.
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
Population: ITT population included all participants who received at least one dose of the study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Progression-Free Survival (PFS) Time | 4.1 months |
Secondary
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.
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
Population: ITT population included all participants who received at least one dose of the study medication. Here number of participants analyzed N is signifying those participants for whom trial treatment failed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU) | Time to Treatment Failure | 4.2 months |