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

NCT01109524 | Completed Phase 2 Results

• 1 other identifier: CA225-346
• Study Type: interventional
• Target: 72
• Locations: 3 countries
• Sites: 22

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.

Conditions

Lung Neoplasms; Carcinoma; Cancer of the Lung; Non-Small-Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (1)

Cetuximab + Cisplatin + Vinorelbine

EXPERIMENTAL

Drug: Cetuximab; Drug: Cisplatin; Drug: Vinorelbine

Interventions

Cetuximab DRUG

Vial, Intravenous, 400mg/m², week 1, then 250mg/m², Weekly, Until Progressive Disease (PD)/ Toxicity/Pt-PI Decision

Also known as: Erbitux, BMS-564717

Cetuximab + Cisplatin + Vinorelbine

Cisplatin DRUG

Vial, Intravenous, 80mg/m², Day 1 of each 21 day cycle, Maximum 6 cycles

Also known as: Platinol

Cetuximab + Cisplatin + Vinorelbine

Vinorelbine DRUG

Vial, Intravenous, 25 mg/m², Day 1 and 8 of each 21 day cycle, Maximum 6 cycles

Also known as: Navelbine

Cetuximab + Cisplatin + Vinorelbine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (22)

Donald W. Hill M.D., P.C.

Casa Grande, Arizona, 85122, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

Cancer Care Institute

Los Angeles, California, 90036, United States

Location

Northern California Hematology & Oncology

Oakland, California, 94609, United States

Location

Sharp Clinical Oncology Research

San Diego, California, 92123, United States

Location

Broward Oncology Associates, P.A.

Fort Lauderdale, Florida, 33308, United States

Location

Elite Research Institute

Miami, Florida, 33125, United States

Location

Edward H. Kaplan, MD & Associates

Skokie, Illinois, 60076, United States

Location

Fairview Southdale Medical Oncology Clinic

Edina, Minnesota, 55435, United States

Location

Mid Dakota Clinic, Pc

Bismarck, North Dakota, 58501, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University Medical Center

Lubbock, Texas, 79415, United States

Location

Columbia Basin Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Local Institution

Grand Falls-Windsor, Newfoundland and Labrador, A2A 2E2, Canada

Location

Sudbury Regional Hospital

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

The Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Thunder Bay Regional Health Sciences Centre (Regional Cancer Care)

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Toronto East General Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Centre de sante et de services sociaux de Rimouski-Neigette

Rimouski, Quebec, G5L 5T1, Canada

Location

Ponce School of Medicine (Caimed Center)

Ponce, 00716, Puerto Rico

Location

Fundacion de Investigacion de Diego

San Juan, 00927, Puerto Rico

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma; Carcinoma, Non-Small-Cell Lung

Interventions

Cetuximab; Cisplatin; Vinorelbine

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2010
• First Posted: April 23, 2010
• Study Start: July 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 24, 2015
• Results First Posted: December 10, 2013

Record last verified: 2015-11

Locations

CA (7); US (13); PR (2)