Safety Study of Cetuximab in Combination With Cisplatin and Vinorelbine to Treat Advanced Non-small Cell Lung Cancer

Cisplatin and Vinorelbine in Combination With Cetuximab as First Line Treatment for Patients With Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC): a Single Arm Multicenter Safety Phase 2 Study

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma; Lung Neoplasms; Non-Small-Cell Lung Carcinoma; Cancer of the Lung
• Intervention / Treatment: Drug: Cetuximab; Drug: Cisplatin; Drug: Vinorelbine

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
  • Newfoundland and Labrador
    • Grand Falls-Windsor, Newfoundland and Labrador, Canada, A2A 2E2
      • Local Institution
  • Ontario
    • Mississauga, Ontario, Canada, L5M 2N1
      • The Credit Valley Hospital
    • Sudbury, Ontario, Canada, P3E 5J1
      • Sudbury Regional Hospital
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences Centre (Regional Cancer Care)
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General Hospital
  • Quebec
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre De Sante Et De Services Sociaux De Rimouski-Neigette
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine (Caimed Center)
  • San Juan, Puerto Rico, 00927
    • Fundacion De Investigacion de Diego
• United States
  • Arizona
    • Casa Grande, Arizona, United States, 85122
      • Donald W. Hill M.D., P.C.
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Los Angeles, California, United States, 90036
      • Cancer Care Institute
    • Oakland, California, United States, 94609
      • Northern California Hematology & Oncology
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology Research
  • Florida
    • Ft. Lauderdale, Florida, United States, 33308
      • Broward Oncology Associates, P.A.
    • Miami, Florida, United States, 33125
      • Elite Research Institute
  • Illinois
    • Skokie, Illinois, United States, 60076
      • Edward H. Kaplan, MD & Associates
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Medical Oncology Clinic
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • Lubbock, Texas, United States, 79415
      • University Medical Center
  • Washington
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cetuximab + Cisplatin + Vinorelbine

Drug: Cetuximab; Vial, Intravenous, 400mg/m², week 1, then 250mg/m², Weekly, Until Progressive Disease (PD)/ Toxicity/Pt-PI Decision; Other Names: Erbitux; BMS-564717; Drug: Cisplatin; Vial, Intravenous, 80mg/m², Day 1 of each 21 day cycle, Maximum 6 cycles; Other Names: Platinol; Drug: Vinorelbine; Vial, Intravenous, 25 mg/m², Day 1 and 8 of each 21 day cycle, Maximum 6 cycles; Other Names: Navelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 up to 30 days after last dose
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.	Day 1 to 30 days after last dose
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.	Day 1 up to 30 days after last dose
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.	Day 2 up to 30 days after last dose
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.	Day 1 up to 30 days after last dose
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.	Day 1 up to 30 days after last dose
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.	Day 1 up to 30 days after last dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: April 22, 2010
• First Submitted That Met QC Criteria: April 22, 2010
• First Posted (Estimate): April 23, 2010

Study Record Updates

• Last Update Posted (Estimate): December 24, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Vinorelbine; Cetuximab
• Other Study ID Numbers: CA225-346