Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic Neuroendocrine Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Part 2: Overall Response Rate
研究概览
简要总结
The goal of this study is to establish maximum tolerated doses/recommended phase 2 dose (RP2D) of temozolomide (TMZ) and TAS-102 when these agents are used in combination and to evaluate the safety profile of this drug combination.
详细描述
The study is a two part phase 1B clinical trial consisting of three study periods: a screening period of 14 days or less, a treatment period, and a safety follow-up period 30 days after treatment discontinuation.
Part 1 is a dose finding phase with the objective to assess the safety and tolerability of the proposed drug combination and to identify the maximum tolerated dose (MTD) and a recommended phase 2 dose.
Part 2 is an open-label expansion study, which will enroll patients with metastatic pNETs who have not been previously treated with chemotherapy. Part 2 will obtain further safety data of the proposed drug combination.
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
- •Part 1: Patients with histologically or cytologically confirmed metastatic or locally advanced NETs of any origin and grade
- •Part 1: Presence of evaluable OR measurable disease
- •Part 2: Patients with histologically confirmed unresectable or metastatic pNETs of grade 1 or
- •Part 2: Presence of measurable disease by RECIST 1.1 criteria
- •Concurrent somatostatin analogues are allowed provided that the dose has been stable (+/- 10mg) for at least 8 weeks
- •Prior chemoembolization or radiation therapy (including Y90) must be performed at least 2 weeks before study enrollment
- •ECOG performance status 0-2
- •Life expectancy more than 3 months
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- •Hemoglobin ≥ 9 g/dL
- •Platelets ≥ 100 x 10^9/L
- •AST/ALT ≤ 3 x ULN (≤5 x ULN in case of liver metastases)
- •Total serum bilirubin of ≤ x institutional ULN (except for Grade 1 hyperbilirubinemia solely due to a medical diagnosis of Gilbert's syndrome)
- •Serum creatinine ≤ 1.5 x institutional ULN (Cockcroft and Gault formula)
- •Ability to take oral medication (i.e. no feeding tube)
- •Female patients of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to the start of the study drug treatment and must agree to use adequate birth control if conception is possible during the study and up to 6 months after discontinuation of study drug treatment
- •Male patients must agree to use adequate birth control during the study and up to 6 months after discontinuation of study drug treatment
- •Women who are nursing must discontinue breast feeding prior to the enrollment in the trial
- •Patient must be able and willing to comply with study procedures as per protocol
- •Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures
排除标准
- •Part 2: Grade 3 tumors or tumors with small cell histology will be excluded
- •Previous treatment with TAS-102 or TMZ
- •History of partial or total gastrectomy
- •Symptomatic CNS metastases requiring treatment
- •Prior radiation therapy irradiating more than 10% of total bone marrow
- •Other active malignancy requiring treatment within the last 2 years (except for non-melanoma skin cancer, a non-invasive/in situ cancer, or indolent nonmetastatic Gleason 6 prostate cancer)
- •Pregnancy or breast feeding
- •Active infection requiring treatment
- •Known chronic infection with human immunodeficiency virus, hepatitis B, or hepatitis C
- •Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration)
- •Any anticancer therapy treatments, including other investigational agents within prior 2 weeks
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102 or TMZ
- •Extended field radiation within prior 4 weeks or limited field radiation within prior 2 weeks
- •Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule
- •Ascites, pleural effusion or pericardial fluid requiring drainage in the last 4 weeks
- •Uncontrolled diabetes mellitus
- •Intestinal obstruction
- •Pulmonary fibrosis
- •Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure NYHA class III or IV
- •Gastrointestinal hemorrhage
研究组 & 干预措施
TAS-102 and TMZ
Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.
Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.
干预措施: TAS-102 (Drug)
TAS-102 and TMZ
Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.
Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.
干预措施: Temozolomide (Drug)
TAS-102 and TMZ
Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.
Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.
干预措施: Filgrastim (Drug)
TAS-102 and TMZ
Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.
Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.
干预措施: Pegfilgrastim (Drug)
结局指标
主要结局
Part 2: Overall Response Rate
时间窗: Up to 5 years
Response rate defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR), assessed as per RECIST criteria. Assessments performed using RECIST criteria.
Part 1: Maximum Tolerated Dose (MTD) of TAS-102
时间窗: Up to 2 years
Investigate the safety and determine the MTD of TAS-102 administered in combination with TMZ in patients with advanced NETs. Treatments will continue to disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST).
次要结局
- Part 2: Disease Control Rate(Up to 5 years)
- Part 2: Duration of Response(Up to 5 years)
- Part 2: Overall Survival(Up to 5 years)
- Part 2: Progression Free Survival (PFS)(Up to 5 years)
- Part 2: Biochemical Response defined as normalization or >50% reduction in levels of Chromogranin A(Up to 5 years)
- Part 2: Safety and Tolerability, Assessed per RECIST Criteria(Up to 5 years)