Phase I Trial of Intratumoral Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta in Patients With Sorafenib Refractory/Intolerant Hepatocellular Carcinoma, Advanced Solid Tumors With Liver Predominant Locally Advanced/Metastatic Disease or Subcutaneous/Cutaneous Lesions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Best tumor response, defined as the best objective status recorded among patients with measurable disease at baseline using Response Evaluation Criteria in Solid Tumors version 1.1
研究概览
简要总结
This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus expressing interferon beta in treating patients with liver cancer or solid tumors with lesions that have spread to other parts of the body and do not respond to treatment. The study virus has a gene inserted into it which will allow production of interferon beta, which is a substance that will restrict the spread of the virus to tumor cells and not healthy cells. It will also have some independent anti-cancer activity. Although the primary goal of this study is to evaluate the safety of delivery of this viral agent to people, patients may benefit clinically by having shrinkage or stabilization of their tumor or reduction in their cancer related symptoms (e.g., pain). Funding Source - FDA OOPD.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing interferon-beta (VSV-IFN-beta) in patients with hepatocellular carcinoma (HCC) refractory or intolerant to sorafenib therapy and patients with advanced solid tumors with liver predominant locally advanced/metastatic treatment refractory disease. (Arm A) II. To determine the maximum tolerated dose (MTD) of VSV-IFN-beta in patients with advanced solid tumors with subcutaneous/cutaneous lesions. (Arm B)
SECONDARY OBJECTIVES:
I. To estimate the tumor response rate, injected lesion (TNi) and distant lesion (TNd) necrosis rate (with TNi and TNd response defined as >= 30% increase in necrosis from baseline) and overall survival. (Arm A)
TERTIARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ARM A: Histologically or cytologically confirmed hepatocellular carcinoma that is refractory (by Response Evaluation Criteria in Solid Tumors [RECIST] or modified [m]RECIST criteria or with unequivocal clinical progression of disease) to or intolerant (defined as inability to administer further sorafenib due to drug related toxicities) of sorafenib based therapy or advanced solid tumor with liver predominant disease burden that has progressed on or is intolerant to standard
- •ARM A: Absolute neutrophil count (ANC) >= 1000/mm^3
- •ARM A: Platelet count >= 80,000/mm^3
- •ARM A: Hemoglobin >= 10 g/dl
- •ARM A: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5 x ULN
- •ARM A: Creatinine =< 1.5 x ULN
- •ARM A: Total bilirubin =< 1.5 x ULN
- •ARM A: International normalized ratio (INR) =< 1.5 x ULN
- •ARM A: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN
- •ARM A: Ability to provide informed written consent
- •ARM A: Willingness to return to Mayo Clinic in Arizona for follow-up
- •ARM A: Life expectancy >= 12 weeks
- •ARM A: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- •ARM A: Willingness to provide all biological specimens as required by the protocol
- •ARM A: Negative serum pregnancy test =< 7 days prior to registration for women of childbearing potential only
- •ARM A: Child Pugh Score A or B7 (patients with ascites must have paracentesis performed within scope of standard of care, to be able to successfully perform intratumoral injection procedure)
- •ARM A: The patient and their partner agree to use a barrier method of contraception during the study and 4 months following end of active treatment
- •ARM A: Disease burden in liver not affecting more than 25% of liver
- •ARM A: Predominant intrahepatic burden (> 75%) of disease (i.e. patients with widespread extrahepatic disease to organs other than the liver will not be included)
- •ARM B: Histologically or cytologically confirmed solid tumor with subcutaneous/cutaneous lesions that is refractory (RECIST or with unequivocal clinical progression of disease) to or intolerant to standard therapy
- •ARM B: Absolute neutrophil count (ANC) >= 1000/mm^3
- •ARM B: Platelet count >= 100,000/mm^3
- •ARM B: Hemoglobin >= 10 g/dl
- •ARM B: AST/ALT =< 2.5 x ULN
- •ARM B: Creatinine =< 1.5 x ULN
- •ARM B: Total bilirubin =< 1.5 x ULN
- •ARM B: INR =< 1.5 x ULN
- •ARM B: aPTT =< 1.5 x ULN
- •ARM B: Ability to provide informed written consent
- •ARM B: Willingness to return to Mayo Clinic in Arizona for follow-up
- •ARM B: Life expectancy >= 12 weeks
- •ARM B: ECOG performance status (PS) 0 or 1
- •ARM B: Willingness to provide all biological specimens as required by the protocol
- •ARM B: Negative serum pregnancy test =< 7 days prior to registration for women of childbearing potential only
- •ARM B: Child Pugh Score A
- •ARM B: The patient and their partner agree to use a barrier method of contraception during the study and 4 months following end of active treatment
- •ARM B: Disease burden in liver not affecting more than 25% of liver
排除标准
- •ARM A: Uncontrolled infection
- •ARM A: Systemic anti-cancer therapy =< 4 weeks prior to registration
- •ARM A: Known human immunodeficiency virus (HIV) infection
- •ARM A: Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy
- •ARM A: Pregnant or nursing women
- •ARM A: History of bone marrow or solid organ transplantation
- •ARM A: Patient for whom surgical resection or liver transplantation would be more appropriate
- •ARM A: Any condition, which in the opinion of the investigator would render the patient unsuitable to participate in the study
- •ARM A: Any corticosteroid use =< 28 days prior to registration
- •ARM A: Any radioembolization or transarterial chemoembolization (TACE) =< 84 days prior to registration
- •ARM B: Uncontrolled infection
- •ARM B: Systemic anti-cancer therapy =< 4 weeks prior to registration
- •ARM B: Known HIV infection
- •ARM B: Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy
- •ARM B: Pregnant or nursing women
- •ARM B: History of bone marrow or solid organ transplantation
- •ARM B: Patient for whom surgical resection or liver transplantation would be more appropriate
- •ARM B: Any condition, which in the opinion of the investigator would render the patient unsuitable to participate in the study
- •ARM B: Any corticosteroid use =< 28 days prior to registration
- •ARM B: Any radioembolization or TACE =< 84 days prior to registration
研究组 & 干预措施
Arm A (viral therapy in single tumor location)
Patients with hepatocellular carcinoma or advanced solid tumor with liver lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in a single tumor location on day 1.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (viral therapy in single tumor location)
Patients with hepatocellular carcinoma or advanced solid tumor with liver lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in a single tumor location on day 1.
干预措施: Pharmacological Study (Other)
Arm A (viral therapy in single tumor location)
Patients with hepatocellular carcinoma or advanced solid tumor with liver lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in a single tumor location on day 1.
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta (Biological)
Arm B (viral therapy in multiple locations)
Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 cutaneous, subcutaneous, or soft tissue tumor lesions on day 1.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (viral therapy in multiple locations)
Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 cutaneous, subcutaneous, or soft tissue tumor lesions on day 1.
干预措施: Pharmacological Study (Other)
Arm B (viral therapy in multiple locations)
Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 cutaneous, subcutaneous, or soft tissue tumor lesions on day 1.
干预措施: Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta (Biological)
结局指标
主要结局
Best tumor response, defined as the best objective status recorded among patients with measurable disease at baseline using Response Evaluation Criteria in Solid Tumors version 1.1
时间窗: From the start of the treatment until disease progression, assessed up to 3 years
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall, by dose level, and by disease type). Examined in an exploratory and hypothesis-generating fashion.
Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
时间窗: Up to 3 years
All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s). The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed by dose level to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Examined in an exploratory and hypothesis-generating fashion.
Maximum tolerated dose, defined as the highest dose at which no more than 1/6 patients experiences dose limiting toxicities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
时间窗: 4 weeks
Dose limiting toxicities defined as an adverse event during the first 4 weeks following injection. A modified "3+3" Fibonacci dose escalation scheme will be used Examined in an exploratory and hypothesis-generating fashion.
Overall survival
时间窗: From registration to death due to any cause, assessed up to 3 years
The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type). Examined in an exploratory and hypothesis-generating fashion.
Tumor necrosis
时间窗: Up to 3 years
Injected lesion and distant lesion necrosis rate will be defined as injected lesion and distant lesion \>= 30% increase in necrosis from baseline, respectively. Frequency and relative frequency will be computed for each (overall, by dose level and by disease type). This analysis will be conducted in hepatocellular carcinoma patients only.
次要结局
未报告次要终点