A Phase 1b/2, Open-label, Randomized Study of MEDI-573 in Combination With Sorafenib Verses Sorafenib Alone in Adult Subjects With Unresectable or Metastatic Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
A Phase 1b/2, open-label, randomized study to evaluate MEDI-573 in combination with standard of care in adult subjects with unresectable or metastatic hepatocellular carcinoma (HCC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years or minimum age of consent per local regulations at the time of screening
- •Unresectable or metastatic hepatocellular carcinoma
- •ECOG Performance Status ≤ 2
- •Life expectancy of ≥ 3 months;
排除标准
- •Child-Pugh Score for Cirrhosis Mortality > 7 points
- •Prior or current system anti-cancer therapy for HCC, including cytotoxic, biologic, targeted or experimental therapy
- •Prior local treatment for HCC less than 4 weeks prior to initiating study treatment
- •Active second malignancy
- •Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to initiating study treatment
- •Thrombotic or embolic events within 6 months prior to initiating study treatment
- •Ongoing pancreatitis
- •Uncontrolled or refractory ascites
- •Evidence of ongoing spinal cord compression, known carcinomatous meningitis, or known leptomeningeal carcinomatosis
- •Hepatic encephalopathy > Grade 1
- •Active brain metastases with exceptions
- •Poorly controlled diabetes mellitus
- •Active coronary artery disease
- •Uncontrolled hypertension
研究组 & 干预措施
Phase 1b Cohort A
Participants will receive MEDI-573 10 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: MEDI-573 (1 of 3 doses) (Drug)
Phase 1b Cohort A
Participants will receive MEDI-573 10 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: Sorafenib (Drug)
Phase 1b Cohort B
Participants will receive MEDI-573 45 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: MEDI-573 (1 of 3 doses) (Drug)
Phase 1b Cohort B
Participants will receive MEDI-573 45 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: Sorafenib (Drug)
Phase 1b Cohort C
Participants will receive MEDI-573 30 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: MEDI-573 (1 of 3 doses) (Drug)
Phase 1b Cohort C
Participants will receive MEDI-573 30 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: Sorafenib (Drug)
Phase 2 Arm 1
Participants will receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: MEDI-573 (1 of 3 doses) (Drug)
Phase 2 Arm 1
Participants will receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: Sorafenib (Drug)
Phase 2 Arm 2
Participants will receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Day 1 to Day 21 of Cycle 1
The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade \< 4 hyperglycemia that resolved in \< 24 hours.
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
时间窗: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
时间窗: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs
时间窗: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
时间窗: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
Phase 2: Time to Progression
时间窗: From Day 1 until documentation of progressive disease (approximately 15 months)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
次要结局
- Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573(Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months))
- Phase 2: Best Overall Tumor Response(From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months))
- Phase 2: Objective Response Rate(From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months))
- Phase 2: Progression-free Survival (PFS)(From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months))
- Phase 2: Change in Tumor Size(From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months))
- Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1(Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose))
- Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1(Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose))
- Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1(Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose))