Cancer of the Lung, Carcinoma, Lung Neoplasms, Non-Small-Cell Lung Carcinoma
Conditions
Brief summary
The purpose of the study is to determine if U.S. manufactured Cetuximab can be safely used for the treatment of Non-Small Cell Lung Cancer in combination with Cisplatin and Vinorelbine.
Interventions
DRUGCetuximab
Vial, Intravenous, 400mg/m², week 1, then 250mg/m², Weekly, Until Progressive Disease (PD)/ Toxicity/Pt-PI Decision
DRUGCisplatin
Vial, Intravenous, 80mg/m², Day 1 of each 21 day cycle, Maximum 6 cycles
DRUGVinorelbine
Vial, Intravenous, 25 mg/m², Day 1 and 8 of each 21 day cycle, Maximum 6 cycles
Sponsors
Eli Lilly and Company
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
* Non-Small Cell Lung Cancer (NSCLC), Stage IV (per the American Joint Committee on Cancer (AJCC) Staging Manual, Seventh Edition) or recurrent disease following surgery and/or radiation therapy * Evaluable or measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion criteria
* Uncontrolled Central Nervous System (CNS) metastasis. * Previous exposure to monoclonal antibodies, signal transduction inhibitors or Epidermal growth factor receptor (EGFR) targeting therapy * Concurrent malignancy * Prior chemotherapy for NSCLC * Pre-existing ascites grade ≥ 2 or pericardial effusion grade ≥ 2 * Superior vena cava syndrome contra-indicating hydration * White Blood Cells (WBC) \< 3,000/mm³ * Absolute neutrophile count (ANC) \< 1,500/mm³ * Platelet \< 100,000/mm³ * Hemoglobin (Hgb) \< 9.0 g/dL * Total bilirubin \> 1.5 x Upper limit of normal (ULN). * Aspartate aminotransferase (AST) or Alanine-aminotransferase (ALT) \> 5.0 x ULN. * Serum creatinine \>1.25 x ULN and calculated creatinine clearance \<60mL/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Day 1 up to 30 days after last dose | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. MedDRA version 14.0. Severity of AEs were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Day 1 (start of study drug) to 30 days after last dose of any treatment therapy, including cetuximab monotherapy. |
| Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Day 1 to 30 days after last dose | Special interest AEs: acneform rash, infusion reaction, cardiac adverse event, febrile neutropenia, infection (includes all terms except sepsis), sepsis, interstitial lung disease, renal failure, and thromboembolic events. Except for interstitial lung disease, these were composite terms combining several preferred/other level MedDRA terms (MedDRA version 14.0). Except for Grade (GR)3 and 4 infusion reactions, AE severity were graded per the NCI-CTC, version 3.0: Gr 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Severity of Gr 3 - 4 infusion reactions were: Gr 3=symptomatic bronchospasm, requiring parenteral medication(s), with or without urticaria; allergy-related edema/angioedema; Gr 4=a life-threatening event characterized by the same symptomatology as a Gr 3, complicated by symptomatic hypotension or oxygen saturation 70% or less. Day 1 (start of study drug) to 30 days after last dose of any treatment therapy, including cetuximab monotherapy. |
| Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | Day 1 up to 30 days after last dose | ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALP=alkaline phosphatase. CTC grade criteria: ALT Grade 1:\>ULN 2.5\*ULN; Grade 2: \>2.5 - 5.0\*ULN; Grade 3: \>5.0 - 20.0\*ULN; Grade 4: \>20.0\*ULN. AST Grade 1: \>ULN - 2.5\*ULN; Grade 2: \>2.5 - 5.0\*ULN; Grade 3: \>5.0 - 20.0\*ULN; Grade 4: \>20.0\*ULN. Total bilirubin Grade 1: \>ULN - 1.5\*ULN; Grade 2: \>1.5 - 3.0\*ULN; Grade 3: \>3.0 - 10.0\*ULN; Grade 4: \>10.0\*ULN. Albumin (low) Grade 1:\<LLN - 3 grams per deciliter (g/dL)to \<LLN - 3 g/dL; Grade 2: \<3 - 2 g/dL to \< 3.0 - 2.0 g/dL; Grade 3: \< 2 g/dL to \<2 g/L. Day 1 (start of study drug) to 30 days after last dose of any treatment therapy, including cetuximab monotherapy. |
| Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Day 2 up to 30 days after last dose | Hematology laboratories included hemoglobin, platelets, white blood cell (WBC) count, and absolute neutrophil count (ANC) and values were per CTC grading, 0, 1, 2, 3, 4. On-study laboratory tests were those performed after the start of study drug (from Day 2 of cycle 1) and up to 30 days after the last dose of study drug. WBC normal range: 4.1-12.3 x 10\^3 /microliter (µL); platelets normal range: 140-450 x 10\^9 /Liter (L); hemoglobin normal range 14-18 grams per deciliter (g/dL); ANC normal range: 2.03-8.36 x 10\^9/μL. |
| Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Day 1 up to 30 days after last dose | ULN=Upper limit of normal among all laboratory ranges; LLN=Lower limit of normal. CTC grade criteria: Sodium high (H) Grade (Gr) 1:\>ULN - 150 millimoles per liter (mmol/L); Gr 2: \>150 - 155 mmol/L; Gr 3: \>155 - 160mmol/L; Gr 4: \>160 mmol/L. Sodium low(L) Gr 1:\<LLN - 130mmol/L; Gr 3: \<130 - 120 mmol/L; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5 mmol/L; Gr 2: \>5.5 - 6.0 mmol/L; Gr 3: \> 6.0 - 7.0 mmol/L; Gr 4: \>7.0 mmol/L. Potassium (L) Gr 1: \<LLN - 3.0 mmol/L; Gr 2: \<LLN - 3.0 mmol/L; Gr 3: \< 3.0 - 2.5 mmol/L; Gr 4: \<2.5 mmol/L. Serum creatinine (H) Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN. Day 1 (start of study drug) to 30 days after last dose of any study drug, including monotherapy. |
| Number of Participants With Drug-Related Treatment-emergent AEs, Drug-Related SAEs, and Drug-Related AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Day 1 up to 30 days after last dose | Drug-related AEs and drug-related SAEs (by investigator assessment) were those with a relationship to study drug(s) reported to Sponsor as related and those of unknown relationship. AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE was defined as a medical event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. MedDRA version 14.0. Severity of AEs were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Day 1 (start of study drug) to 30 days after last dose of any study drug, including monotherapy. |
| Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | Day 1 up to 30 days after last dose | Drug-related AEs (investigator assessment): those with relationship to study drug(s)reported as related and those of unknown relationship. Special interest AEs: acneform rash, infusion reaction, cardiac adverse event, febrile neutropenia, infection (all terms except sepsis), sepsis, interstitial lung disease, renal failure, and thromboembolic events. Except for interstitial lung disease, these were composite terms combining several MedDRA terms (MedDRA version 14.0). Except for Gr 3 and 4 infusion reactions, AE severity per NCI-CTC, version 3.0: Gr 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Gr 3 - 4 infusion reactions: Gr 3=symptomatic bronchospasm, requiring parenteral medication(s), with or without urticaria; allergy-related edema/angioedema; Gr 4=life-threatening event with same Gr 3 symptomatology, complicated by symptomatic hypotension/oxygen saturation 70% or less. Day 1=start of study drug; to 30 days after last dose of any treatment. |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
First participant, first visit: 1 July 2010; Last participant, last visit: 7 September 2012. Participants were chemotherapy-naive with Stage IV histologically or cytologically documented non-small cell lung cancer (NSCLC). Participants treated until: progressive disease (PD)/ toxicity/patient-investigator decision.
Pre-assignment details
72 participants were enrolled and 60 were treated with study drug. 12 not treated: 10 participants no longer met study criteria and 2 participants withdrew consent before entering the treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab + Cisplatin/Vinorelbine Intravenous (IV) cetuximab, 400mg per meter\^2 (m\^2), Week 1, then 250mg/m\^2 weekly, until progressive disease (PD) or toxicity or participant-principal investigator (PPI) decision stopped treatment. One hour of observation required after each infusion. Cisplatin administered as IV solution at initial dose of 80mg/m\^2 on the first day of each 21 day treatment cycle. Vinorelbine administered as IV solution at initial dose of 25 mg/m\^2 on Day 1 and Day 8 of each 21 day treatment cycle. One cycle was defined as a 21-day treatment period, unless chemotherapy administration was delayed (cycle duration was longer). All study drugs discontinued if participants experienced PD. If unacceptable toxicities to any study drug occurred, any drug could be modified (reduced, delayed, omitted, or discontinued) independently of the other drugs If no PD, cetuximab could be given as monotherapy after completion of the 6 treatment cycles or after early discontinuation of cis/vin due to intolerance. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 2 |
| Overall Study | Disease Progression | 29 |
| Overall Study | Maximum clinical benefit | 3 |
| Overall Study | No longer meets criteria | 2 |
| Overall Study | Other | 5 |
| Overall Study | Participant requested to end treatment | 4 |
| Overall Study | Study Drug toxicity | 6 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Cetuximab + Cisplatin/Vinorelbine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 24 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age, Continuous | 63.8 years STANDARD_DEVIATION 10.3 |
| ECOG PS at baseline 0 | 17 Participants |
| ECOG PS at baseline 1 | 38 Participants |
| ECOG PS at baseline 2 | 5 Participants |
| Region of Enrollment Canada | 30 participants |
| Region of Enrollment Puerto Rico | 7 participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 60 |
| serious Total, serious adverse events | 38 / 60 |
Outcome results
Primary
Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. MedDRA version 14.0. Severity of AEs were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Day 1 (start of study drug) to 30 days after last dose of any treatment therapy, including cetuximab monotherapy.
Time frame: Day 1 up to 30 days after last dose
Population: Treated population: all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Deaths due to disease progression | 3 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Deaths due to Other Causes | 2 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | SAE (any grade) | 38 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | AE (any grade) | 59 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | AE Grade 3 or 4 | 46 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Any Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | AE that led to Discontinuation of study drug | 21 participants |
Primary
Number of Participants With Drug-Related Treatment-emergent AEs, Drug-Related SAEs, and Drug-Related AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population
Drug-related AEs and drug-related SAEs (by investigator assessment) were those with a relationship to study drug(s) reported to Sponsor as related and those of unknown relationship. AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE was defined as a medical event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. MedDRA version 14.0. Severity of AEs were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Day 1 (start of study drug) to 30 days after last dose of any study drug, including monotherapy.
Time frame: Day 1 up to 30 days after last dose
Population: Treated population: All participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Drug-Related Treatment-emergent AEs, Drug-Related SAEs, and Drug-Related AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Drug-related SAE (any grade) | 16 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Drug-Related Treatment-emergent AEs, Drug-Related SAEs, and Drug-Related AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Drug-related AE (any grade) | 54 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Drug-Related Treatment-emergent AEs, Drug-Related SAEs, and Drug-Related AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Drug-related AE Grade 3 or 4 | 31 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Drug-Related Treatment-emergent AEs, Drug-Related SAEs, and Drug-Related AEs Leading to Discontinuation of at Least One Study Drug, - Treated Population | Drug-related AE led to Discontinuation of drug | 11 participants |
Primary
Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population
Drug-related AEs (investigator assessment): those with relationship to study drug(s)reported as related and those of unknown relationship. Special interest AEs: acneform rash, infusion reaction, cardiac adverse event, febrile neutropenia, infection (all terms except sepsis), sepsis, interstitial lung disease, renal failure, and thromboembolic events. Except for interstitial lung disease, these were composite terms combining several MedDRA terms (MedDRA version 14.0). Except for Gr 3 and 4 infusion reactions, AE severity per NCI-CTC, version 3.0: Gr 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Gr 3 - 4 infusion reactions: Gr 3=symptomatic bronchospasm, requiring parenteral medication(s), with or without urticaria; allergy-related edema/angioedema; Gr 4=life-threatening event with same Gr 3 symptomatology, complicated by symptomatic hypotension/oxygen saturation 70% or less. Day 1=start of study drug; to 30 days after last dose of any treatment.
Time frame: Day 1 up to 30 days after last dose
Population: Treated population: All participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related acneform rash Grade 3 - 4 | 5 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related infusion reaction Grade 3 - 4 | 2 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related cardiac events Grade 3 - 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related infection Grade 3 - 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related sepsis Grade 3 - 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related interstitial lung disease Grade 3 - 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related renal failure Grade 3 - 4 | 2 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related thromboembolic events Grade 3 - 4 | 5 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Drug-Related Treatment-emergent AEs of Special Interest - Treated Population | drug-related febrile neutropenia Grade 3 - 4 | 4 participants |
Primary
Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population
Special interest AEs: acneform rash, infusion reaction, cardiac adverse event, febrile neutropenia, infection (includes all terms except sepsis), sepsis, interstitial lung disease, renal failure, and thromboembolic events. Except for interstitial lung disease, these were composite terms combining several preferred/other level MedDRA terms (MedDRA version 14.0). Except for Grade (GR)3 and 4 infusion reactions, AE severity were graded per the NCI-CTC, version 3.0: Gr 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Severity of Gr 3 - 4 infusion reactions were: Gr 3=symptomatic bronchospasm, requiring parenteral medication(s), with or without urticaria; allergy-related edema/angioedema; Gr 4=a life-threatening event characterized by the same symptomatology as a Gr 3, complicated by symptomatic hypotension or oxygen saturation 70% or less. Day 1 (start of study drug) to 30 days after last dose of any treatment therapy, including cetuximab monotherapy.
Time frame: Day 1 to 30 days after last dose
Population: Treated population: all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Grade 3-4 acneform rash | 5 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Grade 3-4 infusion reaction | 2 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Cardiac events Grade 3-4 | 3 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Infection Grade 3-4 | 9 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Sepsis Grade 3-4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Renal failure Grade 3-4 | 3 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Thromboembolic events Grade 3-4 | 11 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Interstitial lung disease Grade 3-4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Grades 3 and 4 Treatment-emergent Adverse Events (AEs) of Special Interest - Treated Population | Febrile neutropenia Grade 3-4 | 6 participants |
Primary
Number of Participants With Hematology Laboratory Abnormalities - Treated Population
Hematology laboratories included hemoglobin, platelets, white blood cell (WBC) count, and absolute neutrophil count (ANC) and values were per CTC grading, 0, 1, 2, 3, 4. On-study laboratory tests were those performed after the start of study drug (from Day 2 of cycle 1) and up to 30 days after the last dose of study drug. WBC normal range: 4.1-12.3 x 10\^3 /microliter (µL); platelets normal range: 140-450 x 10\^9 /Liter (L); hemoglobin normal range 14-18 grams per deciliter (g/dL); ANC normal range: 2.03-8.36 x 10\^9/μL.
Time frame: Day 2 up to 30 days after last dose
Population: Treated population: all participants who received at least one dose of any study drug. Participants with at least one on-study laboratory measurement available were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Hemoglobin (low) Grade 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Hemoglobin (low) Grade 1 - 4 | 51 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Hemoglobin (low) Grade 3 or 4 | 4 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Platelets (low) Grade 1 - 4 | 19 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Platelets (low) Grade 3 or 4 | 1 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | Platelets (low) Grade 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | WBC (low) Grade 1 - 4 | 49 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | WBC (low) Grade 3 or 4 | 28 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | WBC (low) Grade 4 | 6 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | ANC (low) Grade 1 - 4 | 47 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | ANC (low) Grade 3 or 4 | 38 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Hematology Laboratory Abnormalities - Treated Population | ANC (low) Grade 4 | 24 participants |
Primary
Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population
ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALP=alkaline phosphatase. CTC grade criteria: ALT Grade 1:\>ULN 2.5\*ULN; Grade 2: \>2.5 - 5.0\*ULN; Grade 3: \>5.0 - 20.0\*ULN; Grade 4: \>20.0\*ULN. AST Grade 1: \>ULN - 2.5\*ULN; Grade 2: \>2.5 - 5.0\*ULN; Grade 3: \>5.0 - 20.0\*ULN; Grade 4: \>20.0\*ULN. Total bilirubin Grade 1: \>ULN - 1.5\*ULN; Grade 2: \>1.5 - 3.0\*ULN; Grade 3: \>3.0 - 10.0\*ULN; Grade 4: \>10.0\*ULN. Albumin (low) Grade 1:\<LLN - 3 grams per deciliter (g/dL)to \<LLN - 3 g/dL; Grade 2: \<3 - 2 g/dL to \< 3.0 - 2.0 g/dL; Grade 3: \< 2 g/dL to \<2 g/L. Day 1 (start of study drug) to 30 days after last dose of any treatment therapy, including cetuximab monotherapy.
Time frame: Day 1 up to 30 days after last dose
Population: Number (N) of participants with laboratory data available and who could be analyzed for total bilirubin was 49. All other liver function laboratories N=57. Treated population: all participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | Albumin (low) Grade 1 - 4 | 37 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | Albumin (low) Grade 3 or 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | Total bilirubin (high) Grade 1 - 4 (N=49) | 3 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | Total bilirubin (high) Grade 3 or 4 (N=49) | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | ALT (high) Grade 1 - 4 | 31 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | ALT (high) Grade 3 or 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | ALP (high) Grade 1 - 4 | 26 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | ALP (high) Grade 3 or 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | AST (high) Grade 1 - 4 | 19 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Liver Function Serum Chemistry Laboratory Abnormalities - Treated Population | AST (high) Grade 3 or 4 | 0 participants |
Primary
Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population
ULN=Upper limit of normal among all laboratory ranges; LLN=Lower limit of normal. CTC grade criteria: Sodium high (H) Grade (Gr) 1:\>ULN - 150 millimoles per liter (mmol/L); Gr 2: \>150 - 155 mmol/L; Gr 3: \>155 - 160mmol/L; Gr 4: \>160 mmol/L. Sodium low(L) Gr 1:\<LLN - 130mmol/L; Gr 3: \<130 - 120 mmol/L; Gr 4: \<120 mmol/L. Potassium (H) Gr 1: \>ULN - 5.5 mmol/L; Gr 2: \>5.5 - 6.0 mmol/L; Gr 3: \> 6.0 - 7.0 mmol/L; Gr 4: \>7.0 mmol/L. Potassium (L) Gr 1: \<LLN - 3.0 mmol/L; Gr 2: \<LLN - 3.0 mmol/L; Gr 3: \< 3.0 - 2.5 mmol/L; Gr 4: \<2.5 mmol/L. Serum creatinine (H) Gr 1: \>1 - 1.5\*baseline (BL)to \>ULN - 1.5\*ULN; Gr 2: \>1.5 - 3.0\*BL to \> 1.5 - 3.0\*ULN; Gr 3: \>3.0\*BL to \> 3.0 - 6.0\*ULN; Gr 4: \>6.0\*ULN. Day 1 (start of study drug) to 30 days after last dose of any study drug, including monotherapy.
Time frame: Day 1 up to 30 days after last dose
Population: Treated population: All participants who received at least one dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Sodium (high) Grade 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Potassium (low) Grade 1 - 4 | 29 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Sodium (low) Grade 1 - 4 | 42 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Sodium (low) Grade 3 or 4 | 18 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Sodium (low) Grade 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Sodium (high) Grade 1 - 4 | 1 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Sodium (high) Grade 3 or 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Potassium (low) Grade 3 or 4 | 12 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Potassium (low) Grade 4 | 1 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Potassium (high) Grade 1 - 4 | 10 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Potassium (high) Grade 3 or 4 | 1 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Potassium (high) Grade 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Serum Creatinine (high) Grade 1 - 4 | 15 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Serum Creatinine (high) Grade 3 or 4 | 0 participants |
| Cetuximab + Cisplatin/Vinorelbine | Number of Participants With Renal Function Serum Chemistry Laboratory Abnormalities - Treated Population | Serum Creatinine (high) Grade 4 | 0 participants |