Multicenter Phase 2 Study of Nintedanib for Patients With Advanced Carcinoid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- PFS
研究概览
简要总结
This phase II trial studies how well nintedanib works in treating patients with neuroendocrine tumors that have spread from where they started to nearby tissue or lymph nodes (locally advanced) or have spread from the primary site (place where they started) to other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by slowing or stopping a certain type of receptor called vascular endothelial growth factor receptor (VEGFR) from attaching to its target. This may stop the growth of neuroendocrine tumors by blocking the growth of new blood vessels necessary for tumor growth.
详细描述
PRIMARY OBJECTIVES:
I. To assess progression free survival (PFS), defined as the time interval from initiation of therapy, to its cessation for documentation of progressive disease (PD) or death.
SECONDARY OBJECTIVES:
I. To assess the clinical response (complete response + partial response) in all patients with measurable disease (using standard Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria).
II. To assess overall survival (OS) in all patients. III. Assess changes in quality of life (QOL) throughout treatment using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) - Gastrointestinal Neuroendocrine Tumors (NET) 21 (GI.NET21) questionnaire for carcinoid patients with gastrointestinal neuroendocrine tumors, in all patients who have filled out at least two QOL questionnaires and, will be reported by groups based on response (response, stable disease or progressive disease).
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
- •Patient must be on a stable dose of octreotide (Sandostatin®) long-acting release (LAR) or lanreotide for 3 months prior to study enrollment
- •Patient must have histologically or cytologically confirmed well differentiated or moderately differentiated (low grade or intermediate grade) neuroendocrine tumor that is locally advanced or metastatic and not of pancreatic origin
- •Measurable disease determined by computed tomography (CT) or magnetic resonance imaging (MRI)
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Life expectancy greater than 3 months
- •Leukocytes >= 3,000/uL
- •Absolute neutrophil count >= 1,500/uL
- •Total bilirubin =< 2 mg/dL
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN) and bilirubin =< ULN for patients without liver metastases
- •AST/ALT =< 2.5 x ULN and bilirubin =< ULN for patients with liver metastases
- •Patients with Gilbert syndrome and bilirubin < 2 x ULN and normal AST/ALT
- •Creatinine =< 1.5 mg/dl
- •Prior treatment will be permitted including surgery (>= 4 weeks), cytotoxic chemotherapy (maximum of 2 prior regimens); radiation, interferon, targeted growth factors (>= 4 weeks); and prior treatment with octreotide, will be allowed
- •Ability to swallow and retain oral medication
- •Participants of child-bearing potential (both male and female) must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- •Archival tissue of carcinoid biopsy must be available
排除标准
- •Uncontrolled hypertension, unstable angina, New York Heart Association grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication, or clinically significant peripheral vascular disease (grade II or greater)
- •Presence of brain metastases
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, or anticipated need for major surgical procedure during the course of the study, or fine needle aspirations or core biopsies within 7 days prior to day 0
- •Significant proteinuria at baseline (>= 500 mg/24 hours [h])
- •Serious non-healing wound, ulcer or bone fracture
- •Evidence of bleeding diathesis or coagulopathy
- •Recent (=< 6 months) arterial thromboembolic events, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction
- •Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoma, or small cell carcinoma
- •Hepatic artery embolization or ablation of hepatic metastasis within 3 months of enrollment, prior peptide receptor radionuclide therapy (PRRT) within 4 months or any other cancer therapy within 4 weeks (as long as all toxicities are resolved)
- •Intolerance or hypersensitivity to octreotide
- •Severe or uncontrolled medical conditions
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or nursing female participants
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (nintedanib)
Patients receive nintedanib PO 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 (nintedanib)
Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Nintedanib (Drug)
Treatment (nintedanib)
Patients receive nintedanib PO 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 (nintedanib)
Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
PFS
时间窗: Time interval from initiation of therapy, to its cessation for documentation of PD or death, assessed up to 2 years
Will be reported using standard Kaplan-Meier methods. Ninety percent confidence intervals for the median PFS will be calculated using Greenwood's formula. Additionally, a confidence interval for the 16-week PFS rate will be obtained using Jeffrey's prior method. The association between survival and quantified variables will be investigated using the Cox-proportional hazard model.
次要结局
- Change in Quality of Life Score(Baseline to 30 days post-treatment)
- Clinical Response (Complete Response + Partial Response) Measured Using Standard RECISTv1.1 Criteria(Up to 2 years)
- Plasma Concentrations at Steady State (Cpre,ss) of Nintedanib at Baseline and Week 8(Baseline to week 8)
- Median OS(Up to 3 years (telephone contact is acceptable).)
- Ratio of FGFR IIIb/IIIc and Ki-67 and Microvessel Density Scores(Baseline)