Japanese Study of Ipilimumab Administered in Combination With Paclitaxel/Carboplatin in Patients With Nonsmall-cell Lung Cancer

NCT01165216 | Completed Phase 1 Results

• 1 other identifier: CA184-113
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study was to establish the recommended dose of ipilimumab administered in combination with paclitaxel and carboplatin in Japanese patients with nonsmall-cell lung cancer.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing a Dose-limiting Toxicity (DLT)

  A DLT was defined as study drug-related adverse event occurring during the first 2 cycles after ipilimumab administration in the induction phase and was any of the following: Grade 4 absolute neutrophil count (ANC) decreased (\<500 cells/ mm\^3) for 7 or more consecutive days; febrile Neutropenia (body temperature ≥38.5° C with ANC \<1000 /mm\^3) lasting \>3 days; Grade 4 platelet count decreased (\<25,000 cells/mm\^3) or Grade 3 platelet count decreased requiring a platelet transfusion; Grade 3 or greater nausea, vomiting, diarrhea, despite the use of adequate/maximal medical intervention; Grade 3 or greater aspartate transaminase/alanine transaminase level and rash that has not resolved to Grade 2 or lower within 2 weeks after onset; or any Grade 3 or greater nonhematologic toxicity (except Grade 3 fatigue, Grade 3 asthenia, Grade 3 transient arthralgia/myalgia, or Grade 3 transient abnormal electrolyte levels).

  Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4

Secondary Outcomes (7)

• Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation

  Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug

• Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease

  Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6

• Maximum Serum Concentration (Cmax) of Ipilimumab

  During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

• Trough Observed Serum Concentration (Cmin) of Ipilimumab

  During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

• Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab

  During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

Study Arms (2)

Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin

EXPERIMENTAL

Participants received ipilimumab, 3 mg/kg, administered as a single dose intravenously (IV) over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, area under the curve (AUC)=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).

Drug: Ipilimumab, 3 mg; Drug: Paclitaxel; Drug: Carboplatin

Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin

EXPERIMENTAL

Participants received ipilimumab, 10 mg/kg, administered as a single dose IV over 90 minutes every 3 weeks, plus paclitaxel, 175 mg/m\^2 , administered as a single dose IV over 3 hours every 3 weeks (up to 6 doses), and carboplatin, AUC=6, administered as a single dose IV over 30-60 minutes every 3 weeks (up to 6 doses).

Drug: Ipilimumab, 10 mg; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Ipilimumab, 3 mg DRUG

Intervenous (IV) injection, administered every 3 weeks for up to 6 cycles

Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin

Ipilimumab, 10 mg DRUG

IV injection, administered every 3 weeks for up to 6 cycles

Also known as: BMS-734016

Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin

Paclitaxel DRUG

IV injection, 175 mg/m\^2, administered every 3 weeks for up to 6 cycles

Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin; Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin

Carboplatin DRUG

IV injection, AUC=6, administered every 3 weeks for up to 6 cycles. (AUC=area under the concentration curve)

Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin; Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented nonsmall-cell lung cancer (NSCLC) presenting as stage IIIB disease without indications for definitive radiotherapy, stage IV disease, or recurrent disease following radiation therapy or surgical resection
• No prior chemotherapy, hormonal therapy, immunotherapy, or targeted-therapy-containing regimens for the treatment of NSCLC
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group performance score of 0-1
• Adequate bone marrow function
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1,500/mm\^3
• Platelet count ≥100,000/mm\^3
• Adequate liver function
• Total bilirubin level ≤2.0\*the upper limit of normal (ULN)
• Asparate aminotransferase level ≤2.5\*ULN
• Alanine aminotransferase level ≤2.5\*ULN
• Adequate renal function
• Calculated creatinine clearance based on Cockcroft and Gault formula ≥50 mL/min.

You may not qualify if:

• Symptomatic central nervous system (CNS) metastasis or active CNS metastasis requiring medication
• Malignant body cavity fluid (eg, pleural effusion, cardiac effusion, ascites) that recurred despite appropriate supportive care
• Prior radiation of ≥30% of major bone-marrow containing areas (pelvis, lumbar spine)
• Documented history of severe autoimmune or immune-mediated symptomatic disease that required prolonged (longer than 2 months) systemic immunosuppressant treatment
• Documented history of motor neuropathy considered of autoimmune origin (eg, Guillain Barré syndrome)
• Any concurrent malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, carcinoma of the mucous membrane of the gastrointestinal tract, or superficial bladder cancer treated with systemic therapy
• ≥Grade 2 diarrhea
• History of or concurrent disease of gastrointestinal tract perforations
• ≥Grade 2 peripheral neuropathy (motor or sensory)
• Uncontrolled intercurrent illness including infection requiring systemic therapy, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled angina pectoris, uncontrolled peptic ulcer, and cardiac arrhythmia requiring medication
• Positive finding for human immunodeficiency virus antibody, hepatitis B surface antigen, or hepatitis C virus antibody.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Local Institution

Chuo-ku, Tokyo, 1040045, Japan

Location

Related Publications (1)

• Horinouchi H, Yamamoto N, Fujiwara Y, Sekine I, Nokihara H, Kubota K, Kanda S, Yagishita S, Wakui H, Kitazono S, Mizugaki H, Tokudome T, Tamura T. Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer. Invest New Drugs. 2015 Aug;33(4):881-9. doi: 10.1007/s10637-015-0243-5. Epub 2015 May 1.

  PMID: 25924991 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ipilimumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2010
• First Posted: July 19, 2010
• Study Start: September 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 22, 2014
• Results First Posted: July 22, 2014

Record last verified: 2014-06

Locations

JP (1)