Clinical trial NCT01165216: Japanese Study of Ipilimumab Administered in Combination With Paclitaxel/Carboplatin in Patients With Nonsmall-cell Lung Cancer
Official title: Phase 1 Study of Ipilimumab (BMS-734016) in Combination With Paclitaxel and Carboplatin in Japanese Patients With Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-07-19
Enrollment: 15
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
timeFrame: Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4
Secondary outcomes:
measure: 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
timeFrame: Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug
measure: Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease
timeFrame: Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6
measure: Maximum Serum Concentration (Cmax) of Ipilimumab
timeFrame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
measure: Trough Observed Serum Concentration (Cmin) of Ipilimumab
timeFrame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
measure: Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab
timeFrame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
measure: Time of Maximum Observed Serum Concentration (Tmax)
timeFrame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
measure: Serum Half-life (T-HALF) of Ipilimumab
timeFrame: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
Other outcomes:
Locations:
city: Chuo-ku
country: Japan
facility: Local Institution
state: Tokyo
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.