NCT04829383已完成2 期
A Phase II Study of Atezolizumab and Bevacizumab in Child-Pugh B7 and B8 Hepatocellular Carcinoma (The AB7 Trial)
Howard S Hochster13 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2021年3月22日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 13
- 主要终点
- Frequency and severity of toxicities
研究概览
简要总结
This will be a nonrandomized, single arm feasibility study with the primary goal of evaluating the safety profile of the combination of atezolizumab and bevacizumab in patients with advanced/metastatic HCC with Child-Pugh B7 and B8 liver disease who have received no prior systemic therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Subject must meet all of the following applicable inclusion criteria to participate in this study:
- •Written informed consent and HIPAA authorization for release of personal health information must be obtained either from the subject or their representative. See protocol. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-
- •Locally advanced, metastatic, or unresectable hepatocellular carcinoma that has not received prior systemic therapy. Note: if no prior histologic diagnosis exists, prefer fresh biopsy if it is both safe and feasible. If fresh biopsy is not safe and feasible, imaging criteria may be used for diagnosis as per AASLD criteria in cirrhotic patients (please see www.aasld.org for up to date guidelines).
- •Child Pugh Class B7 or B8 liver dysfunction or cirrhosis with the following limitations:
- •Bilirubin ≤ 3 mg/dL
- •Albumin ≥ 2.8 g/dL
- •INR ≤ 1.7
- •Absent to slight [CP=1 to 2] (no moderate [CP=3]) ascites (Also see
排除标准
- •No clinically significant encephalopathy (Also see exclusion criteria).
- •At least 1 untreated measurable lesion according to RECIST 1.
- •Willingness to undergo fresh tumor biopsy at baseline if safe and feasible. Note: archival tissue may be used at baseline provided histologic diagnosis was made and sufficient tissue is available for NGS analysis.
- •NGS analysis must be requested from archival tissue or fresh biopsy (if applicable) as per standard of care. Foundation One CDX is the preferred platform. Prior NGS sequencing results (including from another platform) will be accepted if NGS sequencing was previously obtained (please see protocol).
- •Demonstrate adequate bone marrow and organ function as defined below:
- •Hematologic
- •Absolute neutrophil count (ANC) ≥ 1,000/mcL
- •Lymphocyte count ≥ 0.5 x 10^9/L (500uL)
- •Hemoglobin ≥ 90 g/L (9 g/dL)
- •Platelet count ≥ 70,000/mcL
- •Serum creatinine OR calculated* serum creatinine clearance (GFR can be used in place of creatinine or creatinine clearance) ≤ 1.5 x ULN OR ≥ 30 mL/min for participants with creatinine levels > 1.5 x institutional ULN *calculate serum creatinine clearance using the standard Coccroft-Gault formula
- •Urine protein: Urine dipstick for proteinuria < 2+ within 7 days prior to start of study treatment *Patients with with ≥ 2+ proteinuria on dipstick analysis at baseline should undergo a 24-hour urine collection which must demonstrate < 1g of protein in 24 hours.
- •AST (SGOT) and ALT (SGPT) ≤ 8 x ULN
- •Alkaline phosphastase (ALP) ≤ 8 x ULN
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, or 6 months after the last dose of bevacizumab. See also the protocol for definition of childbearing potential.
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use effective contraceptive measures. Men with female partners of childbearing potential must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of bevacizumab. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of bevacizumab to avoid exposing the embryo. See also the protocol for additional information.
- •As determined by the enrolling physician or protocol designee, ability of the subject to understand a written informed consent document, and ability and willingness to comply with study procedures for the entire length of the study. Patients with impaired decision-making capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) and/or family member available are also eligible.
- •Exclusion Criteria:
- •Subjects meeting any of the criteria below may not participate in the study:
- •Histologic diagnosis of fibrolamellar or sarcomatoid HCC or mixed cholangiocarcinoma-HCC.
- •Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 21 days of first planned dose of study therapy (within 14 days for palliative radiation). Patients who have had major surgery within 4 weeks of start of study therapy or anticipation of need for a major surgical procedure during the study.
- •Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > CTCAE Grade 1) with the exception of alopecia or neuropathy.
- •Patients who have received prior systemic therapy for HCC.
- •Patients who have received prior immunotherapy.
- •Patients with clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control within 3 months prior to the first dose of study treatment. Note: Patients with ascites meeting eligibility criteria who require pharmacologic intervention (e.g. diuretics) to maintain symptomatic control and who have been on stable doses of diuretics for 2 months prior to the first dose of study treatment are eligible.
- •Patients with clinically meaningful encephalopathy, defined as a history of hepatic encephalopathy within 6 months prior to first dose of study treatment or requirement for medications to prevent or control encephalopathy (e.g. lactulose, rifaximin).
- •Any of the following additional high-risk features:
- •Patients with untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. Note: Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD with appropriate management of varices (if applicable) within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
- •History of esophageal and/or gastric hemorrhage within 3 months prior to study treatment.
- •History of hemoptysis (< 2.5 mL of bright red blood per episode) within 1 month prior to study treatment.
- •History of intracranial hemorrhage within 1 month prior to study treatment.
- •History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment. Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure.
- •Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture within 30 days prior to start of study treatment.
- •Metastatic disease that involves major airways or blood vessels. Patients with vascular invasion of the portal or hepatic veins may be enrolled.
- •Significant vascular disease (e.g. aortic aneurysm requiring surgical repair) or vasculitis within 6 months prior to initiation of study treatment.
- •History of arterial thrombotic event (e.g. myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack) within 6 months prior to initiation of study treatment.
- •Chronic or recent (within 10 days of first dose of study treatment) use of aspirin > 325 mg/day, dipyramidaole, ticlopidine, clopidogrel, or dilostazol. Note: Use of aspirin < 325 mg/day is allowed.
- •History of venous thromboembolic event (e.g. deep vein thrombosis, pulmonary embolism, portal vein thrombosis, or any other significant thromboembolism) must be on a stable dose of anticoagulation for 1 month prior to initiation of study treatment and must have completely treated varices.
- •Use of Coumadin-like products or full dose oral or parenteral anticoagulants. Use of prophylactic low dose anticoagulation, unfractionated heparin or LMWH is allowed.
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- •Core biopsy or other minor surgical procedure within 3 days prior to the first dose of bevacizumab.
- •History of intestinal obstruction. Note: Patients with previous intestinal obstruction may be enrolled if they have received definitive treatment for symptom resolution.
- •History of inflammatory process within 6 months prior to start of study treatment including but not limited to active peptic ulcer disease, diverticulitis or colitis.
- •Significant traumatic injury within 4 weeks prior to start of study treatment.
- •Uncontrolled pleural effusion or pericardial effusion requiring frequent drainage procedures (> once monthly). Patients with indwelling catheters (e.g. PleurX®) are allowed.
- •History of nephrotic or nephritic syndrome.
- •Uncontrolled hypertension defined as systolic pressure ≥ 150/90 in spite of maximum anti-hypertensive therapy.
- •Patients with untreated/uncontrolled CNS/leptomeningeal disease. Note: Patients with asymptomatic, treated CNS disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy and the following criteria are met:
- •No evidence of interim progression between the completion of CNS-directed therapy and the start of study enrollment.
- •No stereotactic radiation or whole-brain radiation within 28 days prior to randomization.
- 另有 31 项未显示
研究组 & 干预措施
Study Treatment
Experimental
Atezolizumab 1,200 mg IV and bevacizumab 15 mg/kg IV every 3 weeks (on day 1 of each 21-day cycle). Treatment will continue until disease progression or development of unacceptable toxicity.
干预措施: Atezolizumab (Drug)
Study Treatment
Experimental
Atezolizumab 1,200 mg IV and bevacizumab 15 mg/kg IV every 3 weeks (on day 1 of each 21-day cycle). Treatment will continue until disease progression or development of unacceptable toxicity.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Frequency and severity of toxicities
时间窗: 1 year
Grade 3-5 treatment-related adverse event rate according to CTCAE v5
Grade 3-5 Adverse Events
时间窗: Adverse Events have been recorded from the time of consent until 30 days after treatment discontinuation of study drugs or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 10 months
Number of participants with grade 3-5 treatment-related adverse event reported by CTCAE v5 term and grade
次要结局
- Duration of response (DOR)(1 year)
- Disease control rate (DCR)(1 year)
- Median progression-free survival (PFS)(1 year)
- Median overall survival (OS)(1 year)
- Overall response rate (ORR)(1 year)
- Overall Response Rate (ORR)(Up to a maximum of 11 months)
- Disease Control Rate (DCR)(Up to a maximum of 11 months.)
- Duration of Response (DOR)(Up to a maximum of 11 months)
- Overall Survival (OS)(Up to a maximum of 11 months.)
- Progression-free Survival (PFS)(Up to a maximum of 11 months.)
研究者
Howard S Hochster
Sponsor-Investigator
Big Ten Cancer Research Consortium
研究点 (13)
Loading locations...
相似试验
Unknown
2 期
Atezolizumab Monotherapy and Consequent Therapy With Atezolizumab Plus Bevacizumab for NSCLCNon Small Cell Lung CancerNCT03616691Samsung Medical Center46
招募中
2 期
Atezolizumab/Bevacizumab Followed by On-demand TACE or Initial Synchronous Treatment With TACE and Atezolizumab/BevacizumabHepatocellular Carcinoma Non-resectableNCT04224636Ludwig-Maximilians - University of Munich106
终止
2 期
Atezolizumab and Bevacizumab in EGFR Mutant NSCLC in Patients With Progressive Disease After Receiving OsimertinibNon Small Cell Lung CancerNCT04099836Duke University7
进行中（未招募）
不适用
Atezolizumab Plus Bevacizumab With HCC and HBV InfectionCarcinoma, HepatocellularNCT04180072National Health Research Institutes, Taiwan51
进行中（未招募）
2 期
Clinical Trial of Atezolizumab With Paclitaxel, Trastuzumab, and Pertuzumab in Patients With Metastatic HER-2 Positive Breast CancerHER2-positive Breast CancerNCT03125928Fox Chase Cancer Center16