A MULTICENTER, GLOBAL, RANDOMIZED, DOUBLE-BLIND STUDY OF AXITINIB PLUS BEST SUPPORTIVE CARE VERSUS PLACEBO PLUS BEST SUPPORTIVE CARE IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA FOLLOWING FAILURE OF ONE PRIOR ANTIANGIOGENIC THERAPY
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 224
- 试验地点
- 76
- 主要终点
- Overall Survival (OS) - Stratified Analysis, Randomized Portion
研究概览
简要总结
The study is designed to demonstrate that axitinib plus best supportive care is superior to placebo plus best supportive care in prolonging survival in patients with advanced hepatocellular carcinoma.
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
- Double (Participant, Investigator)
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
- •Locally advanced or metastatic HCC
- •Failure of one prior antiangiogenic therapy including sorafenib, bevacizumab and brivanib.
- •Child-Pugh Class A or B (score 7 only) disease.
排除标准
- •Prior treatment of advanced HCC with more than one prior first-line systemic therapy.
- •Any prior local therapy within 2 weeks of starting the study treatment.
- •Presence of hepatic encephalopathy and/or clinically relevant ascites.
- •Presence of main portal vein invasion by HCC.
研究组 & 干预措施
A
Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non-randomized portion. Study treatment was administered in cycles of 4 weeks in duration
干预措施: Axitinib (AG-013736) (Drug)
A
Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non-randomized portion. Study treatment was administered in cycles of 4 weeks in duration
干预措施: Best Supportive Care (Other)
B
Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child-Pugh Class B, score 7, were not permitted to enter the randomized portion of the study
干预措施: Placebo (Drug)
B
Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child-Pugh Class B, score 7, were not permitted to enter the randomized portion of the study
干预措施: Best Supportive Care (Other)
结局指标
主要结局
Overall Survival (OS) - Stratified Analysis, Randomized Portion
时间窗: From randomization until at least two years after the last participant has been randomized (up to 6 years)
OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - first randomization date +1)/30.4. For participants still alive at the time of the analysis, the OS time was censored on the last date they were known to be alive. All participants were followed up for survival at least every 3 months after discontinuing study treatment until at least two years after randomization of the last participant.
次要结局
- Axitinib Steady-State PK Parameter - Area Under the Plasma Concentration Versus Time Curve From 0 to 24 Hour (AUC0-24), Non-Randomized Portion(Cycle 1 Day 15)
- Progression-Free Survival (PFS) - Stratified Analysis, Randomized Portion(Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first)
- Objective Response Rate (ORR) - Percentage of Participants With Objective Response by Stratified Analysis, Randomized Portion(Every 8 weeks until at least two years after the last participant has been randomized)
- Time to Tumor Progression (TTP) - Stratified Analysis, Randomized Portion(Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first)
- Duration of Response (DR) by Unstratified Analysis, Randomized Portion(From objective response to date of progression or death)
- Percentage of Participants With Overall Clinical Benefit Response (CBR) - Stratified Analysis, Randomized Portion(From Baseline up to end of treatment)
- Axitinib Steady-State Pharmacokinetic (PK) Parameter - Maximum Observed Plasma Concentration (Cmax), Non-Randomized Portion(Cycle 1 Day 15)
- Axitinib Steady-State Pharmacokinetic Parameter - Time to First Occurrence of Cmax (Tmax), Non-Randomized Portion(Cycle 1 Day 15)
- Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Clearance (CL/F), Non-Randomized Portion(Cycle 1 Day 15)
- Axitinib Steady-State Pharmacokinetic Parameter - Terminal Plasma Elimination Half-Life (t1/2), Non-Randomized Portion(Cycle 1 Day 15)
- Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Volume of Distribution of the Drug During the Elimination Phase (Vz/F), Non-Randomized Portion(Cycle 1 Day 15)
- Concentration of Soluble Proteins at Baseline in Randomized Portion(Baseline)
- Percentage of Participants With Specific Micro-Ribonucleic Acid (miRNA) Transcript Present in Circulation in Randomized Portion(Baseline)
- Functional Assessment of Cancer Therapy - Hepatobiliary Questionnaire (FACT-Hep) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Functional Assessment of Cancer Therapy - General (FACT-G) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Functional Assessment of Cancer Therapy (FACT)-Hepatobiliary Symptom Index-8 (FHSI-8) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Functional Assessment of Cancer Therapy-G (FACT-G) Subscales in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Subscale (FACT Hep-CS18) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Trial Outcome Index (FACT Hep-TOI) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Time to Deterioration (TTD) Based on the Composite Endpoint in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(From randomization to death or tumor progression or FHSI-8 mean score decrease >=3 points, whichever comes first)
- EuroQoL (EQ-5D)- Health State Profile Utility Score in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- EuroQoL Visual Analogue Scale (EQ-VAS) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model(Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date)
- Number of Participants With Dose-Limiting Toxicities (DLTs) in Non-Randomized Portion(Cycle 1 (4 weeks))
- Number of Participants With Treatment-Emergent Adverse Events (AEs) in Non-Randomized Portion(Up to 28 days after last dose of study drug (up to 6 years))
- Number of Participants With Treatment-Related Adverse Events (AEs) in Non-Randomized Portion(Up to 28 days after last dose of study drug (up to 6 years))
- Number of Participants With Treatment-Emergent Adverse Events (AEs) in Randomized Portion(Up to 28 days after last dose of study drug (up to 6 years))
- Number of Participants With Treatment-Related Adverse Events (AEs) in Randomized Portion(Up to 28 days after last dose of study drug (up to 6 years))