NCT03382886终止1 期
A Phase I Open Label Trial of a Combination of Nivolumab and Bevacizumab in Patients With Advanced and or Metastatic Hepatocellular Carcinoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Adverse Events that occur
研究概览
简要总结
This is an open label, phase I study to test for maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of the combination of nivolumab and bevacizumab. The study will use a 3+3 phase I study design using a fixed dose of nivolumab (240mg) and escalating doses of bevacizumab (1-10mg).
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
- •Confirmed unresectable or metastatic hepatocellular carcinoma. Confirmation either by histologic confirmation or accepted radiographic criteria.
- •Received at least one line of therapy with a TKI (including, but not limited to sorafenib, lenvatinib, and/or regorafenib) with evidence of disease progression clinically or radiographically as deemed by investigator, or refused therapy with a TKI. No more than two lines of prior therapy are allowed.
- •Measurable disease per RECIST1.
- •Age ≥18 years.
- •ECOG performance status of 0 to
- •Life expectancy ≥ 12 weeks.
- •Childs Pugh A (5-6 points). Demonstrate adequate organ function as defined in the table below
- •Hematologic:
- •Absolute neutrophil count (ANC) ≥ 1.5 k/µL. Platelets ≥ 100 k/µL Hemoglobin ≥ 9 g/dL
- •Creatinine < 2 × ULN OR
- •Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
排除标准
- •Prior treatment with anti-PD1 or anti-PD-L1 antibody therapy.
- •Subjects with a prior history of DVT/PE, who have not been on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks.
- •History of arterial thromboembolic event in past 6 months (including CVA, MI).
- •Systemic anti-cancer treatment within 2 weeks, all ongoing adverse events related to previous systemic anti-cancer therapy resolved to grade ≤
- •Radiotherapy within 2 weeks of first dose of study medications.
- •Major surgery within 6 weeks of first dose of study medications. Minor procedures (e.g. port placement, endoscopy with intervention) within 4 weeks of first dose of study medications.
- •Presence of ≥ CTCAE grade 2 toxicity due to prior cancer therapy (except alopecia, peripheral neuropathy which are excluded if ≥ CTCAE grade 3).
- •Medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication.
- •Active ongoing infection requiring therapy.
- •Active HIV infection.
- •History of severe hypersensitivity reaction to another monoclonal antibody.
- •Active central nervous system metastases and/or carcinomatous meningitis (stable treated brain metastases not requiring steroids >4 weeks allowed).
- •Cardiac conditions: class 3-4 New York Heart Association congestive heart failure, known baseline LVEF < 50%, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past 12 months.
- •Any history of autoimmune disease requiring treatment in the past 5 years or felt to be at risk to reactivate autoimmune disease. Patients who are felt to no longer be at risk of activating a known autoimmune disease (e.g. type 1 diabetes, ulcerative colitis s/p complete colectomy, autoimmune thyroiditis s/p thyroidectomy or medical ablation, etc.) may be allowed to participate after discussion with the PI
- •Pregnant, breast feeding, or planning to become pregnant.
- •Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- •Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five half-lives. Contraception as described in section 7.3
- •Received any live vaccine within the last 30 days.
- •Other malignancy requiring treatment in the prior 2 years with the exception of locally treated squamous or basal cell carcinoma.
研究组 & 干预措施
Nivolumab and bevacizumab, all patients
Experimental
干预措施: Nivolumab (Drug)
Nivolumab and bevacizumab, all patients
Experimental
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Adverse Events that occur
时间窗: Every 14 day cycle for up to 2 years - Patients are expected to be on treatment for an average of 6 months
Investigate the safety and tolerability of 14-day cycles of nivolumab plus bevacizumab. Adverse events will be collected for each subject that received the study treatment combination.
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
时间窗: The DLT period will begin at Cycle 1 Day 1 and continue through Cycle 1 Day 28 for each patient
Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Dose Limiting Toxicities (DLT) will define subsequent subject accrual and dose escalation
次要结局
- Progression Free Survival (PFS)(3 years after treatment stops)
- Overall Survival(3 years after treatment stops)
研究者
研究点 (1)
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