Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Cisplatin in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 6
- 主要终点
- Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])
研究概览
简要总结
The primary purpose of this study is to help answer the following research question(s):
- To see how the body absorbs, processes, and gets rid of cetuximab when the drug is taken in combination with cisplatin [pharmacokinetic (PK) analysis]
- To see if any drug interactions occur between cetuximab and cisplatin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant has histologically or cytologically advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy.
- •The participant has measurable or non-measurable disease.
- •The participant has a life expectancy of greater than 3 months.
- •The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •The participant has adequate hematologic function as defined by absolute neutrophil count greater than or equal to 1500/microliter (μL), hemoglobin greater than or equal to 9 grams/deciliter (g/dL), and platelet count greater than or equal to 100,000/μL.
- •The participant has adequate hepatic function as defined by a total bilirubin less than or equal to 2 x the upper limit of normal (ULN), aspartate transaminase (AST, SGOT) and alanine transaminase (ALT, SGPT) less than or equal to 3 x the ULN (or less than or equal to 5 x the ULN in the presence of known liver metastases).
- •The participant has adequate renal function as defined by serum creatinine less than or equal to 1.5 x the institutional ULN or creatinine clearance greater than or equal to 60 mL/min for participants with creatinine levels above the ULN.
- •The participant has the ability to understand, and the willingness to sign, a written informed consent document.
- •If the participant has received prior therapy with platinum, the time to the first treatment of study drug from the last platinum exposure is >28 days.
排除标准
- •The participant has symptomatic brain or leptomeningeal metastasis.
- •The participant has not recovered from Adverse Events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have improved to Grade less than 2 per the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 3.
- •The participant is receiving any other investigational agent(s).
- •The participant is receiving concurrent treatment with other anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy (RT), chemoembolization, or targeted therapy. Participants receiving palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible.
- •The participant is receiving therapy with immunosuppressive agents.
- •The participant has known drug or alcohol abuse.
- •The participant has uncontrolled hypertension defined as systolic blood pressure greater than or equal to 180 millimeters of mercury (mm Hg) or diastolic blood pressure greater than or equal to 130 mm Hg.
- •The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or cisplatin.
- •The participant has a medical or psychological condition that would not permit the participant to complete the study or sign informed consent.
- •The participant has clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
- •The participant, if female, is pregnant (confirmed by serum or urine beta-human chorionic gonadotropin [β-HCG] pregnancy test) or breastfeeding
- •The participant has had a known positive test result for the human immunodeficiency virus.
- •The participant has an active infection (requiring intravenous [IV] antibiotics), including tuberculosis.
研究组 & 干预措施
Cetuximab and Cisplatin (D)
Cycle 1 (1 week, combination therapy):
400 milligrams per square meter (mg/m²) cetuximab administered (admin) intravenously (I.V) on week 1, day 1.
100 mg/m² cisplatin administered I.V on week 1, day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/m²/day (d) administered starting on week 1, day 1.
After 1 cycle, participants may continue treatment as determined by the physician until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cetuximab (Drug)
Cetuximab and Cisplatin (D)
Cycle 1 (1 week, combination therapy):
400 milligrams per square meter (mg/m²) cetuximab administered (admin) intravenously (I.V) on week 1, day 1.
100 mg/m² cisplatin administered I.V on week 1, day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/m²/day (d) administered starting on week 1, day 1.
After 1 cycle, participants may continue treatment as determined by the physician until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cisplatin (Drug)
Cetuximab and Cisplatin (D)
Cycle 1 (1 week, combination therapy):
400 milligrams per square meter (mg/m²) cetuximab administered (admin) intravenously (I.V) on week 1, day 1.
100 mg/m² cisplatin administered I.V on week 1, day 1. Optional 5- fluorouracil (FU) administered as a 96-hour continuous infusion (C.I.) of 1000 mg/m²/day (d) administered starting on week 1, day 1.
After 1 cycle, participants may continue treatment as determined by the physician until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: 5 - Fluorouracil (Drug)
Cetuximab and Cisplatin (C)
Cycle 1 (4 weeks, combination therapy):
100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1.
Cycle 2-6 (3 weeks combination therapy):
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, day 1.
After 6 cycles, participants may then receive weekly cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cetuximab (Drug)
Cetuximab and Cisplatin (C)
Cycle 1 (4 weeks, combination therapy):
100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1.
Cycle 2-6 (3 weeks combination therapy):
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, day 1.
After 6 cycles, participants may then receive weekly cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cisplatin (Drug)
Cetuximab and Cisplatin (C)
Cycle 1 (4 weeks, combination therapy):
100 mg/m² Cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3 and 4, day 1.
Cycle 2-6 (3 weeks combination therapy):
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 1, 2, and 3, day 1.
After 6 cycles, participants may then receive weekly cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: 5 - Fluorouracil (Drug)
Cetuximab on Cisplatin (B)
Cycle 1:
400 mg/m² cetuximab admin I.V on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 2 and 3, day 1.
Cycle 2:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1- 4.
250 mg/m² cetuximab admin I.V on week 1-3, day 1.
Cycle 3 + :
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
250 mg/m² cetuximab admin I.V on week 1-3, day 1.
After 6 cycles, participants may then receive weekly cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cetuximab (Drug)
Cetuximab on Cisplatin (B)
Cycle 1:
400 mg/m² cetuximab admin I.V on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 2 and 3, day 1.
Cycle 2:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1- 4.
250 mg/m² cetuximab admin I.V on week 1-3, day 1.
Cycle 3 + :
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
250 mg/m² cetuximab admin I.V on week 1-3, day 1.
After 6 cycles, participants may then receive weekly cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cisplatin (Drug)
Cetuximab on Cisplatin (B)
Cycle 1:
400 mg/m² cetuximab admin I.V on week 1, day 1. 250 mg/m² cetuximab admin I.V on week 2 and 3, day 1.
Cycle 2:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1- 4.
250 mg/m² cetuximab admin I.V on week 1-3, day 1.
Cycle 3 + :
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
250 mg/m² cetuximab admin I.V on week 1-3, day 1.
After 6 cycles, participants may then receive weekly cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: 5 - Fluorouracil (Drug)
Cisplatin on Cetuximab (A)
Cycle 1:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1.
Cycle 2 +:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
250 mg/m² cetuximab admin I.V on weeks 1-3, day 1.
After 7 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cetuximab (Drug)
Cisplatin on Cetuximab (A)
Cycle 1:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1.
Cycle 2 +:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
250 mg/m² cetuximab admin I.V on weeks 1-3, day 1.
After 7 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: Cisplatin (Drug)
Cisplatin on Cetuximab (A)
Cycle 1:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
400 mg/m² cetuximab admin I.V on week 2, day 1. 250 mg/m² cetuximab admin I.V on week 3, day 1.
Cycle 2 +:
100 mg/m² cisplatin admin I.V on week 1, day 1. 5- FU admin as a 96-hour C.I. of 1000 mg/m²/d admin starting on week 1, day 1-4.
250 mg/m² cetuximab admin I.V on weeks 1-3, day 1.
After 7 cycles, participants may then receive weekly Cetuximab monotherapy until progression of disease, unacceptable toxicity, or another withdrawal criterion is met.
Due to protocol amendment in September 2011, any newly enrolled participants were placed into cetuximab and cisplatin (C) arm only. After protocol amendment February 2014, any newly enrolled participants will be placed into cetuximab and cisplatin (D) arm only.
干预措施: 5 - Fluorouracil (Drug)
结局指标
主要结局
Total Cisplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])
时间窗: Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).
Cetuximab Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)
时间窗: Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion).
Cetuximab Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)
时间窗: Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion).
Total Cisplatin Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
时间窗: Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).
Cetuximab Pharmacokinetics: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
时间窗: Group B:Cycle 1,Day 15 and Cycle 2, Day 1 and Group C: Cycle 1, Day 22 and Cycle 2, Day 1: Baseline (Prior to Cetuximab Infusion),1, 2, 4, 8, 24, 72, 120, and 168 hours (After the Start of Cetuximab Infusion).
Total Cisplatin Pharmacokinetics: Measurement of the Time After Administration When the Maximum Plasma Concentration is Reached (Tmax)
时间窗: Groups A and C: Cycle 1,Day 1 and Cycle 2 Day 1; Baseline (Prior to Cisplatin Infusion), 1, 1.50, 2, 3, 5, 8, 24, 72 hours (After the Start of Cisplatin Infusion).
Cetuximab Pharmacokinetics: Confirmatory Serum Concentration
时间窗: Group D:Cycle 1, Day 1: Prior to Cisplatin Infusion.
次要结局
未报告次要终点