Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
antitumor activity, safety, cetuximab in combination with radiotherapy, locally advanced squamous cell head & neck carcinoma
Brief summary
Primary objective: to assess the antitumor activity and safety profile of cetuximab when given in combination with radiotherapy (RT) for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in Chinese subjects. Secondary objective: to assess the pharmacokinetic (PK) profile and immunogenicity of cetuximab in Chinese subjects. Further objective: to identify for cetuximab potential predictive biomarkers of response and safety.
Interventions
BIOLOGICALCetuximab + concomitant boost radiotherapy
Cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially * Once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by * Twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses are separated by at least a 6-hour interval
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
* Inpatient greater than or equal to (\>=) 18 years of age * Pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx or larynx * Stage III or IV disease with an expected survival of at least 12 months * Medically suitable to withstand a course of concomitant boost RT * Presence of at least 1 bi-dimensionally measurable lesion identified either by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to modified World Health Organization (WHO) criteria * Karnofsky Performance Status (KPS) \>=80 at trial entry * Neutrophils \>=1.5\*10\^9/Liter (L), platelet count \>= 100\*10\^9/L, hemoglobin \>= 90 gram/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/liter (mcmol/L) * Serum calcium within normal range * Effective contraception if procreative potential exists (applicable to both male and female subjects) * Chinese with Chinese citizenship * Signed written informed consent
Exclusion criteria
* Evidence of distant metastatic disease * Squamous cell carcinoma arising in the nasopharynx or oral cavity * Receipt of prior systemic chemotherapy within the last 3 years * Previous surgery for the tumor under study other than biopsy * Receipt of prior RT to the head and neck * Currently receiving RT as part of a postoperative regimen following primary surgical resection * Planned neck dissection after trial RT * 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 * Previous treatment with monoclonal antibody therapy, other signal transduction inhibitors or epidermal growth factor receptor (EGFR) targeting therapy * Evidence of previous other malignancy within the last 5 years * Intake of any investigational medication within 30 days before trial entry * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit | Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline up to disease progression or withdrawal or 12 weeks after the last radiotherapy of the last participant | Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later). |
Countries
China
Participant flow
Pre-assignment details
A total of 70 participants were screened, out of which 4 participants were not treated and 66 participants received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. | 66 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Another Anti-cancer Drug Received | 1 |
| Overall Study | Another Tumor Discovered | 1 |
| Overall Study | Death | 14 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Ongoing | 29 |
| Overall Study | Progressive Disease (PD) | 18 |
| Overall Study | Symptomatic Deterioration | 1 |
Baseline characteristics
| Characteristic | Cetuximab |
|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 9.5 |
| Age, Customized <65 years | 52 participants |
| Age, Customized >=65 years | 14 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 64 / 66 | 20 / 62 |
| serious Total, serious adverse events | 5 / 66 | 14 / 62 |
Outcome results
Primary
Best Overall Response (BOR)
Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD.
Time frame: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit
Population: Intention-to-treat (ITT) population included all participants who received at least one dose of the investigational medicinal product (IMP) cetuximab or RT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Best Overall Response (BOR) | 68.2 percentage of participants |
Secondary
Progression-Free Survival (PFS)
Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later).
Time frame: Baseline up to disease progression or withdrawal or 12 weeks after the last radiotherapy of the last participant
Population: ITT population included all participants who received at least one dose of the IMP cetuximab or RT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Progression-Free Survival (PFS) | 9.4 months |