A Phase I Study to Determine the Safety of the Combination of Stable-Emulsion Formulation of Glucopyranosyl Lipid A (GLA-SE) With Radiation in Patients With Metastatic Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Incidence of severe adverse events, defined as any grade 3 or higher adverse event (AE) according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
研究概览
简要总结
This pilot phase I clinical trial studies the side effects and best dose of toll-like receptor 4 (TLR4) agonist glucopyranosyl lipid A (GLA)-stable-emulsion (SE) when given together with radiation therapy in treating patients with soft tissue sarcoma that has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). TLR4 agonist GLA-SE may stimulate the immune system to kill sarcoma cells. Radiation therapy uses high energy x rays to kill tumor cells. Giving TLR4 agonist GLA-SE with radiation therapy may be a better treatment to treat sarcoma that cannot be removed by surgery.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety of weekly injections of GLA-SE (TLR4 agonist GLA-SE) in combination with palliative radiation in patients with metastatic sarcoma.
SECONDARY OBJECTIVES:
I. To look for preliminary evidence of efficacy at distant tumor sites following the combination of radiation and intra-tumor injection of GLA-SE.
II. To analyze changes in tumor-immune infiltrates following radiation and intra-tumor injection of GLA-SE.
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
- •A diagnosis of metastatic or unresectable sarcoma
- •Patient must have a palpable, superficial tumor, safely accessible for bedside injection that will be radiated and can be accurately localized and stabilized if needed
- •Patient must have consulted with a radiation oncologist who is planning radiation; radiation should be completed within a 2-week window from start to finish
- •Patient must be willing to undergo biopsies as specified by the protocol; the biopsy requirement can only be waived if deemed unsafe by the patient's treating physician or the principal investigator (PI)
- •Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status of '0-2'
- •Serum creatinine =< 1.5 times the upper limit of normal
- •Total bilirubin =< 1.5 times the upper limit of normal
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal
- •Prothrombin time (PT) =< 1.5 times the upper limit of normal
- •Partial thromboplastin time (PTT) =< 1.5 times the upper limit of normal
- •Absolute neutrophil > 1000/uL
- •Platelet count > 75,000/uL
- •For patients who will be entering the "expansion phase" of the trial, the patient must be able to safely delay radiation by at least 6 weeks
排除标准
- •Pregnant women, nursing women, men and women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to study entry
- •Known active symptomatic congestive heart failure
- •Known clinically significant hypotension
- •Known newly diagnosed cardiac arrhythmia; patients with an arrhythmia that has been stable for at least 3 months will be allowed to participate
- •Known untreated central nervous system (CNS) metastasis
- •Patients with known systemic infections requiring antibiotics or chronic maintenance/suppressive therapy
- •Systemic anticancer therapy (chemotherapy, "biologics", immunotherapy) less than two weeks prior to starting radiation
- •Known clinically significant autoimmune disorders requiring on-going systemic immune-suppression for control
- •Current treatment with steroids
- •Patients who are known to be human immunodeficiency virus (HIV) positive must have a normal cluster of differentiation (CD)4 count and undetectable viral load
- •Current treatment with warfarin; for patients not on an anti-platelet agent such as aspirin, other anticoagulation is acceptable so long as the treating physician feels that it is safe to hold it on the day of the biopsy until after the biopsy has been safely completed
- •Known allergy(ies) to any component of the study agent GLA-SE including egg lecithin
研究组 & 干预措施
Treatment (TLR4 agonist GLA-SE, radiation therapy)
Patients receive TLR4 agonist GLA-SE intratumorally once weekly for 8 weeks. Within 2 weeks of starting treatment, patients also undergo radiation therapy over 2 weeks for a total of 5-6 fractions.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (TLR4 agonist GLA-SE, radiation therapy)
Patients receive TLR4 agonist GLA-SE intratumorally once weekly for 8 weeks. Within 2 weeks of starting treatment, patients also undergo radiation therapy over 2 weeks for a total of 5-6 fractions.
干预措施: Radiation Therapy (Radiation)
Treatment (TLR4 agonist GLA-SE, radiation therapy)
Patients receive TLR4 agonist GLA-SE intratumorally once weekly for 8 weeks. Within 2 weeks of starting treatment, patients also undergo radiation therapy over 2 weeks for a total of 5-6 fractions.
干预措施: TLR4 Agonist GLA-SE (Drug)
结局指标
主要结局
Incidence of severe adverse events, defined as any grade 3 or higher adverse event (AE) according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
时间窗: Up to week 9
The highest toxicity grades per patient will be tabulated for AEs and laboratory measurements as will the numbers and percentages of patients reporting AEs.
次要结局
- Change in biomarker outcomes from the peripheral blood(Baseline up to 1 year)
- Clinical benefit based on RECIST v1.1 and iRRC evaluations(Up to 1 year)
- Immune infiltrates, measured quantitatively as number of cells per unit area(Up to 1 year)
- Progression free survival(Up to 1 year)
- Response based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 and immune-related-response criteria (iRRC) evaluations(Up to 1 year)
- Survival(Up to 1 year)
- Time to progression(Up to 1 year)