NCT01303341进行中（未招募）1 期
A Phase I Trial of Riluzole and Sorafenib in Patients With Advanced Solid Tumors and Melanoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose of sorafenib tosylate and riluzole in patients with all types of solid tumors
研究概览
简要总结
This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with riluzole in treating patients with solid tumors or melanoma that has spread to other places in the body and usually cannot be cured or controlled with treatment. Riluzole may stop or slow the growth of tumor cells. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving riluzole together with sorafenib tosylate may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To define a safe dose of sorafenib (sorafenib tosylate) to combine with riluzole in the treatment of patients with all types of solid tumors refractory to standard therapy or for whom no standard therapy exists.
SECONDARY OBJECTIVES:
I. To examine the correlation of clinical or radiologic response with signaling through the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways.
II. To determine if response to therapy with riluzole and sorafenib correlates with expression levels of B-cell lymphoma (BCL)-2, myeloid cell leukemia (MCL)-1, or BCL2-like 11 (apoptosis facilitator) (BIM).
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
- •Patients must have histologically proven solid tumors (Phase I) with biopsiable tumor (expansion cohort) refractory to standard therapy or for whom no standard therapy exists or who decline standard therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Patients must be willing and able to sign informed consent
- •Unlimited prior therapies are permitted for patients enrolled in the dose escalation phase of the study; patients in the expansion cohort of the study may not have any prior therapy with riluzole or sorafenib and must have biopsiable tumor
- •Patients may have measurable or evaluable disease
- •Absolute neutrophil count (ANC) >= 1,500/uL
- •Platelets >= 100,000/uL
- •Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
- •International normalized ratio (INR) =< 1.5 x institutional ULN
- •Creatinine =< 2 x ULN
- •Patients with brain lesions that have been treated with whole brain radiotherapy and are clinically stable for at least 4 weeks, are not taking steroids and are not receiving enzyme-inducing anticonvulsants will be eligible
排除标准
- •Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
- •For patients who have received gamma knife or stereotactic radiosurgery, a 2 week washout is required; patients who have had other types of radiotherapy, chemotherapy or biologic agents within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier to =< grade 1; at least 4 weeks must have elapsed since any major surgery; patients with prostate cancer may continue to receive hormonal therapy
- •History of allergic reactions attributed to riluzole or sorafenib
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 2 weeks after discontinuation of riluzole and/or sorafenib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; pregnant (positive pregnancy test) or lactating patients cannot participate
- •Known human immunodeficiency virus (HIV) infection or known history of active hepatitis B or C infection
- •Current, recent (within 4 weeks of the first treatment of this study), or planned participation in an experimental drug study (prevention trials are permitted if the trial is not testing a novel experimental agent)
- •Cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- •History of stroke within six months
- •Clinically significant peripheral vascular disease
- •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- •Uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg, despite optimal medical management
- •Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
- •Any of the following within 6 months prior to first dose of treatment: myocardial infarction, symptomatic coronary artery disease (severe or unstable angina), artery bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolus
- •Pulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first-dose of study drug
- •Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug
- •Evidence or history of bleeding diathesis or coagulopathy
- •Major surgery or significant traumatic injury within 4 weeks of first study drug
- •The eligibility of patients taking medications that are potent modulators of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), subfamily 2, polypeptide 8 (2C8) will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications
- •Any condition that impairs the patient's ability to swallow whole pills
- •Any malabsorption problem
- •Anticipation of need for major surgical procedure during the course of the study
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of treatment
- •Serious, non-healing wound, ulcer, or bone fracture
- •Inability to comply with study and/or follow-up procedures
- •Anticoagulation with Lovenox (enoxaparin) is permitted, however, patients on anticoagulation with warfarin are not permitted on this study
研究组 & 干预措施
Treatment (riluzole and sorafenib tosylate)
Experimental
Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (riluzole and sorafenib tosylate)
Experimental
Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Riluzole (Drug)
Treatment (riluzole and sorafenib tosylate)
Experimental
Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (riluzole and sorafenib tosylate)
Experimental
Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Sorafenib Tosylate (Drug)
结局指标
主要结局
Maximum-tolerated dose of sorafenib tosylate and riluzole in patients with all types of solid tumors
时间窗: 28 days
Maximum tolerated dose is defined as the first dose level at which exactly 2/6 patients experience dose limiting toxicity, or at which 1/6 experience dose limiting toxicity and (due to de-escalation) at least 2/3 or 3/6 patients treated with the next higher dose level had dose limiting toxicity.
次要结局
- Suppression of MAPK and PI3K/AKT pathways(Up to 3 years)
- Change in BCL-2 expression(Baseline to 3 years)
- Change in MCL-1 expression(Baseline to 3 years)
- Change in BIM expression(Baseline to 3 years)
- Pharmacokinetic parameters of the combination of riluzole with sorafenib tosylate(On days 2, 8, 10, and 15 of each course)
- Change in microvesicle quantification(Baseline to 3 years)
研究者
研究点 (1)
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