A Ph 2 Study to Investigate the Safety and Activity of Fosbretabulin Tromethamine (CA4P) in the Treatment of Well-Differentiated, Low-to-Intermediate-Grade Unresectable, Recurrent or Metastatic PNET or GI-NET Neuroendocrine Tumors/Carcinoid With Elevated Biomarkers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 5
- 主要终点
- Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline
研究概览
简要总结
This study will investigate the safety, symptoms and biomarker response of subjects with biopsy-proven well-differentiated, low-to-intermediate-grade, unresectable, or metastatic pancreatic neuroendocrine tumors (PNETs) or or Gastrointestinal Neuroendocrine tumors (GI-NETs) with elevated biochemical markers who have relapsed during or after receiving prior standard of care therapies, including octreotide, chemotherapy or targeted therapy.
详细描述
Subjects enrolled in this PNET/GI-NET study (OX4218s) will receive weekly dosing with fosbretabulin for up to 3 cycles or approximately 9 weeks.
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
- •Ability to read, understand and provide written consent to participate in the study
- •Age ≥ 18 years
- •Biopsy-proven well-differentiated, low-to-intermediate-grade PNET or GI-NET with elevated (> ULN) biomarkers (serotonin, 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A (CgA), neurokinin A, and neuron-specific enolase (NSE))
- •Life expectancy > 12 weeks
- •Must have received or may still be receiving one or more therapies including octreotide or serotonin synthesis inhibitor (SSI) or other somatostatin analogues
- •Confirmed progressive disease within 18 months of enrollment on study
- •Recovered from prior radiation therapy or surgery
- •Eastern Cooperative Oncology Group (ECOG) performance score 0-2
- •Absolute neutrophil count (ANC) ≥ 1,500/µL (without growth factors)
- •Platelet count ≥ 100,000/µL
- •Adequate renal function as evidenced by serum creatinine
- •≤ 2.0 mg/dL (177 µmol/L)
- •Adequate hepatic function: serum total bilirubin ≤ 2X greater than the upper limit of normal (ULN) (≤ 3X ULN in subjects with liver metastases), aspartate aminotransferase) AST) / alanine aminotransferase (AST) ≤ 2X the ULN for the local reference lab (≤ 5X the ULN for subjects with liver metastases)
- •Disease that can be assessed (evaluable) with imaging (CT, MRI, PET, radionuclide imaging or other imaging modality)
- •Women of childbearing potential as well as fertile men and their partners must use an effective method of birth control
排除标准
- •Inadequately controlled hypertension defined as BP > 150/100 mm Hg despite medication
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Recent history (within 6 months of start of screening) of unstable angina pectoris pattern, myocardial infarction (including non-Q wave MI), or NYHA (New York Heart Association) Class III and IV Congestive Heart Failure (CHF)
- •Subjects who have clinical evidence of carcinoid-induced heart disease
- •History of prior cerebrovascular accident (CVA), including transient ischemic attach (TIA)
- •Known central nervous system (CNS) disease except for treated brain metastasis
- •History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
- •Corrected QT interval (QTc) > 480 msec
- •Ongoing treatment with any drugs known to prolong the QTc interval, including anti-arrhythmic medications (stable regimen of antidepressants of the selective serotonin reuptake inhibitor (SSRI) class is allowed))
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Significant vascular disease or recent peripheral arterial thrombosis
- •Known intolerance of or hypersensitivity to fosbretabulin
- •History of solid organ transplant or bone marrow transplant
- •Any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
- •High grade or poorly differentiated NET
- •NET tumor other than PNET or GI-NET
- •No elevated biomarker (>ULN) that can be followed
- •Received regional hepatic infusion therapy within 6 months of enrollment (RFA allowed >6 months prior to enrollment)
研究组 & 干预措施
fosbretabulin tromethamine
Fosbretabulin 90 mg/vial; 60 mg/m2, IV infusion over 10 minutes; 1x/wk; three 3-week cycles
干预措施: fosbretabulin tromethamine (Drug)
结局指标
主要结局
Number of Participants With Improved, Stable, or Worsened Change In Chromogranin A (CgA) Biomarker Levels From Baseline
时间窗: Baseline and 4 months
The mean change from baseline in chromogranin A (CgA) biomarker level is considered improved if a 25% reduction occurs and worsened if the mean change from baseline is increased by 25%.
Number of Participants With Improved, Stable, or Worsened Change In 5-hydroxyindoleacetic Acid (5-HIAA) Biomarker Levels From Baseline
时间窗: Baseline and 4 months
The mean change from baseline in 5-hydroxyindoleacetic acid (5-HIAA) biomarker level is considered improved if a 25% reduction occurs and worsened if the mean change from baseline is increased by 25%.
Number of Participants With Improved, Stable, or Worsened Change In Serotonin Biomarker Levels From Baseline
时间窗: Baseline and 4 months
The mean change from baseline in serotonin biomarker level is considered improved if a 25% reduction occurs and worsened if the mean change from baseline is increased by 25%.
次要结局
- Number of Participants With Partial Response (PR), Progressive Disease (PD), or Stable Disease (SD) Based on RECIST 1.1(Baseline and 4 months)