Japanese Study of Ipilimumab Administered in Combination With Paclitaxel/Carboplatin in Patients With Nonsmall-cell Lung Cancer
2014年6月23日 更新者：Bristol-Myers Squibb
Phase 1 Study of Ipilimumab (BMS-734016) in Combination With Paclitaxel and Carboplatin in Japanese Patients With Non-Small Cell Lung Cancer
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.
調査の概要
研究の種類
介入
入学 (実際)
15
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Tokyo
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Chuo-ku、Tokyo、日本、1040045
- Local Institution
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
16年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin
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).
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Intervenous (IV) injection, administered every 3 weeks for up to 6 cycles
IV injection, 175 mg/m^2, administered every 3 weeks for up to 6 cycles
IV injection, AUC=6, administered every 3 weeks for up to 6 cycles.
(AUC=area under the concentration curve)
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実験的：Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin
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).
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IV injection, 175 mg/m^2, administered every 3 weeks for up to 6 cycles
IV injection, AUC=6, administered every 3 weeks for up to 6 cycles.
(AUC=area under the concentration curve)
IV injection, administered every 3 weeks for up to 6 cycles
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
時間枠：Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4
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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).
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Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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
時間枠：Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose 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.
Treatment-related=having certain, probable, possible, or unknown relationship to study drug.
AE incidence was assessed from Day 1 until Week 24 and every 12 weeks thereafter during the maintenance period, until discontinuation of study drug, due to progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure, and at least every 4 weeks(±1 week) until all study drug-related toxicities had recovered to resolved, stabilized or returned to baseline or were deemed irreversible during the follow-up period).
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Continuously from Day 1 to Week 24 and every12 weeks thereafter during maintenance until discontinuation of drug
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Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease
時間枠：Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6
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Tumor response was determined for all participants with measurable lesions by radiologic responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
The BOR was the best response recorded from start of treatment until disease progression/recurrence.
RECIST for target lesions: PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.
At minimum, tumor measurements were to be obtained at screening, every 6 weeks (±1 week) during the induction phase and every 12 weeks (±1 week) during the maintenance phase.
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Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6
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Maximum Serum Concentration (Cmax) of Ipilimumab
時間枠：During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Cmax was recorded directly from experimental observations.
Actual times were used for the analyses.
Cmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.
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During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Trough Observed Serum Concentration (Cmin) of Ipilimumab
時間枠：During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Cmin was recorded directly from experimental observations.
Actual times were used for the analyses.
Cmin measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 (Day 8), and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure.
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During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab
時間枠：During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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The AUC(0-21d) was calculated using a mixture of log- and linear-trapezoidal summations.
Using no weighting factor, the terminal log-liner phase of the concentration-time curve was determined by least-square linear regression of at least 3 data points.
Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods using a validated PK analysis program.
Actual times were used for the analyses.
AUC(0-21d) measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure.
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During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Time of Maximum Observed Serum Concentration (Tmax)
時間枠：During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Tmax was recorded directly from experimental observations.
Actual times were used for the analyses.
Tmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.
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During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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Serum Half-life (T-HALF) of Ipilimumab
時間枠：During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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T-HALF was calculated as the ratio of ln(2) to elimination rate constant (K), where K was estimated as negative slope obtained by regression of the terminal log-linear portion of the serum concentration vs time profile following the ipilimumab dose on Day 1 of Cycle 3. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods, using a validated PK analysis program.
Actual times were used for the analyses.
T-HALF measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure.
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During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2010年9月1日
一次修了 (実際)
2013年6月1日
研究の完了 (実際)
2013年6月1日
試験登録日
最初に提出
2010年7月16日
QC基準を満たした最初の提出物
2010年7月16日
最初の投稿 (見積もり)
2010年7月19日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年7月22日
QC基準を満たした最後の更新が送信されました
2014年6月23日
最終確認日
2014年6月1日
詳しくは
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