A Study to Evaluate the Relationship Between Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
研究概览
简要总结
The purpose of this study is to determine if Ramucirumab (IMC-1121B) causes prolongation of the QT/QTc interval in participants with advanced cancer.
详细描述
The primary purpose of this study is to determine if treatment with ramucirumab causes prolongation of the QTc/QT interval in participants with advanced cancer, to assess the safety and tolerability of ramucirumab therapy, and to evaluate the pharmacokinetic (PK) characteristics of ramucirumab
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 documented advanced or metastatic malignant cancer of solid tumor origin which has not responded to standard therapy or for which no standard therapy is available
- •The participant has resolution of adverse events from prior anticancer therapies
- •Performance status of 0 to 2
- •The participant is ≥ 18 years of age
- •The participant is able to provide informed written consent and is amenable to compliance with protocol schedules and testing
- •The participant has adequate liver, kidney, blood, and blood clotting functions as defined in trial entrance criteria
- •The participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment
排除标准
- •The participant had anticancer therapy within 14 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- •The participant had therapeutic radiotherapy within 14 days prior to entering the study
- •The participant has ongoing side effects ≥ Grade 2 due to prior anticancer therapy
- •The participant has brain or leptomeningeal metastases
- •The participant has a history of uncontrolled or severe cardiac disease
- •The participant has a history of severe congestive heart failure (CHF)
- •The participant has a known history of arterial thrombotic events
- •The participant has a known history of significant peripheral arterial disease (PAD)
- •The participant has an implantable pacemaker or automatic implantable cardioverter defibrillator (AICD)
- •The participant has a history of risk factors for ventricular tachycardia or Torsades de pointes (TdP) [for example, family history (parents or siblings) of long QT syndrome], history of fainting, unexplained loss of consciousness, or convulsions
- •The participant has a systolic blood pressure (SBP) of > 150 millimeters of mercury (mmHg) or < 90 mmHg or a diastolic blood pressure (DBP) of < 45 or > 95 mmHg. (Participants with a history of hypertension who are receiving antihypertensive therapy are permitted on study provided blood pressure is within the parameters detailed above)
- •The participant has a heart rate < 50 beats per minute (bpm) or > 100 bpm at rest
- •The participant has a clinically relevant abnormality on the ECG, preventing an accurate measurement of the QT interval
- •The participant is using a medication that is known to prolong the ECG QT interval
- •The participant has a known allergy to any of the treatment components including fluoroquinolone antibiotics
- •The participant has received an investigational new drug or device within 14 days prior to enrollment into this study (excluding placement of an intravenous access device)
- •The participant has undergone major surgery within 28 days prior to enrollment
- •The participant has known human immunodeficiency virus (HIV) infection
- •The participant, if female, is pregnant or lactating
- •The participant is receiving chronic daily treatment with aspirin [> 325 milligrams per day (mg/day)]
- •The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm
- •The participant has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent
研究组 & 干预措施
IMC-1121B
Active-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period.
For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab [10 milligrams per kilogram (mg/kg)] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.
干预措施: IMC-1121B (Biological)
IMC-1121B
Active-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period.
For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab [10 milligrams per kilogram (mg/kg)] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.
干预措施: Moxifloxacin (Drug)
IMC-1121B
Active-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period.
For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab [10 milligrams per kilogram (mg/kg)] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.
干预措施: Diphenhydramine (Drug)
结局指标
主要结局
Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants
时间窗: Baseline, Cycle 3 (1 cycle=21 days)
All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR\^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.
次要结局
- Number of Participants With Drug-Related Adverse Events (AEs)(Baseline up to data cut off (approximately 105.6 weeks))
- Maximum Concentration (Cmax) During Cycle 1(Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose])
- Maximum Concentration (Cmax) During Cycle 1, Day 4(Approximately Week 1 (Cycle 1, Day 4))
- Maximum Concentration (Cmax) During Cycle 1, Day 8(Approximately Week 2 (Cycle 1, Day 8))
- Maximum Concentration (Cmax) During Cycle 1, Day 15(Approximately Week 3 (Cycle 1, Day 15))
- Maximum Concentration (Cmax) During Cycle 2(Cycle 2 (predose and 1.25 hours postdose))
- Maximum Concentration (Cmax) During Cycle 3(Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose])
- Area Under Concentration (AUC) During Cycle 1(Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose])
- Area Under Concentration (AUC) During Cycle 1, Day 4(Approximately Week 1 (Cycle 1, Day 4))
- Area Under Concentration (AUC) During Cycle 1, Day 8(Approximately Week 2 (Cycle 1, Day 8))
- Area Under Concentration (AUC) During Cycle 1, Day 15(Approximately Week 3 (Cycle 1, Day 15))
- Area Under Concentration (AUC) During Cycle 2, Day 1(Approximately Week 1 (Cycle 2, Day 1))
- Area Under Concentration (AUC) During Cycle 3(Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose])