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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01109524
First received: April 22, 2010
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Lung Neoplasms
Carcinoma
Cancer of the Lung
Non-Small-Cell Lung Carcinoma
Drug: Cetuximab
Drug: Cisplatin
Drug: Vinorelbine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 1 up to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 2 up to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 30 days after last dose ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 72
Study Start Date: July 2010
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Platinol
Drug: Vinorelbine
Vial, Intravenous, 25 mg/m², Day 1 and 8 of each 21 day cycle, Maximum 6 cycles
Other Name: Navelbine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01109524

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

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01109524     History of Changes
Other Study ID Numbers: CA225-346
Study First Received: April 22, 2010
Results First Received: September 12, 2013
Last Updated: November 15, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Canada: Canadian Institutes of Health Research
Canada: Ethics Review Committee

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cetuximab
Cisplatin
Vinorelbine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014