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

Lung Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109524
• Other study ID #: CA225-346
• Status: Completed
• Phase: Phase 2
• First received: April 22, 2010
• Last updated: November 24, 2015
• Start date: July 2010
• Est. completion date: September 2012

Study information

• Verified date: November 2015
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationCanada: Canadian Institutes of Health ResearchCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer of the Lung
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Carcinoma

Intervention

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

Locations

Country	Name	City	State
Canada	Local Institution	Grand Falls-Windsor	Newfoundland and Labrador
Canada	The Credit Valley Hospital	Mississauga	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	Centre de sante et de services sociaux de Rimouski-Neigette	Rimouski	Quebec
Canada	Sudbury Regional Hospital	Sudbury	Ontario
Canada	Thunder Bay Regional Health Sciences Centre (Regional Cancer Care)	Thunder Bay	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Puerto Rico	Ponce School of Medicine (Caimed Center)	Ponce
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Mid Dakota Clinic, Pc	Bismarck	North Dakota
United States	Donald W. Hill M.D., P.C.	Casa Grande	Arizona
United States	Fairview Southdale Medical Oncology Clinic	Edina	Minnesota
United States	Broward Oncology Associates, P.A.	Ft. Lauderdale	Florida
United States	Columbia Basin Hematology and Oncology	Kennewick	Washington
United States	Cancer Care Institute	Los Angeles	California
United States	University Medical Center	Lubbock	Texas
United States	Elite Research Institute	Miami	Florida
United States	Northern California Hematology & Oncology	Oakland	California
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Sharp Clinical Oncology Research	San Diego	California
United States	Edward H. Kaplan, MD & Associates	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 up to 30 days after last dose	Yes
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.	Day 1 to 30 days after last dose	Yes
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:	Day 1 up to 30 days after last dose	Yes
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.	Day 2 up to 30 days after last dose	Yes
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:	Day 1 up to 30 days after last dose	Yes
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.	Day 1 up to 30 days after last dose	Yes
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.	Day 1 up to 30 days after last dose	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form