NCT01365910终止2 期
An Investigator Initiated, Phase II Study of Linifanib in Patients With Advanced, Refractory Colorectal Cancer Expressing Mutated kRas
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15%
研究概览
简要总结
This phase II trial studies how well Linifanib works in treating patients with advanced, refractory colorectal cancer expressing k-Ras mutations. Linifanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To achieve an overall response rate of 15% or more.
SECONDARY OBJECTIVES:
I. Determine progression free survival. II. Determine overall survival. III. Evaluate toxicity profile of ABT 869 (linifanib) in this patient population.
OUTLINE:
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
- •Histologically confirmed colorectal cancer refractory to at least 1 but no more than 3 systemic chemotherapy regimens
- •Patients must have received one standard chemotherapy regimen in the metastatic setting
- •Established Ras-mutant tumor status (archived specimens are okay and this test can have been performed at local laboratories)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •The subject must have adequate bone marrow and organ function, defined as follows:
- •Hemoglobin ≥ 9g/dL
- •Platelets >100,000,
- •Absolute neutrophil count (ANC) > 1000/uL,
- •Serum creatinine < 1.5 x upper limit of normal,
- •Total bilirubin < 1.5 x the upper limit of normal,
- •AST and ALT ≤ 2.0 x upper limit of normal (or ≤ 5 x ULN in the presence of liver metastases)
- •Measurable disease, defined as at least 1 unidimensionally measurable lesion on a computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days of study treatment; surgically sterile and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-child-bearing potential
- •Female subjects of child-bearing potential and male subjects must agree to use adequate contraception prior to study entry, for the duration of study participation and up to two months after the last dose of ABT 869; adequate contraception methods should be used consistently and correctly and include the following:
- •Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
- •A vasectomized partner
- •Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
- •Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
- •The subject must be willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations
- •The subject must have given written informed consent prior to the initiation of any screening or study-specific procedures
- •Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study-specific procedures
- •Patients must be at least 14 days status post last day of prior chemotherapy (at least 28 days since last dose of bevacizumab) and have recovered to grade =< 1 from all chemotherapy-associated side effects
- •Patients must have the ability to swallow pills
排除标准
- •Untreated central nervous system (CNS) metastases; patients may have CNS metastases from any timeframe as long as they are treated and not progressing; brain imaging is not required if there is no clinical suspicion of brain metastases
- •Pregnant or lactating females are excluded
- •Uncontrolled hypertension defined as systolic blood pressure (BP) > 140 and/or diastolic BP > 90 initially evaluated on day of study eligibility determination (when laboratory parameters are assessed), but must be maintained on day of study initiation; (If a patient is found to have a value outside the range above, repeat BP may be assessed and if at subsequent readings x 2 (taken in clinic at least 15 minutes apart) criteria are met, the patient can then be eligible; initiation or modification of antihypertensives is allowed to achieve adequate BP for eligibility; finally, in the case that subsequent determinations are required, the BP assessment that counts towards eligibility is the reading on the day of study initiation); (note: a clinic BP reading without the patient having been at rest for 15 minutes or with the wrong cuff size can be repeated the same day for eligibility criteria to be determined
- •Active bleeding or history of bleeding from cancer related events
- •History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) or recent myocardial infarction (MI) (< 6 months)
- •Active ulcerative colitis, Crohn's disease or Celiac disease that could interfere with the absorption of the drug
- •Current use of therapeutic anticoagulation; low dose anticoagulation for catheter prophylaxis is permitted; Lovenox is permitted for prophylaxis; (Note: patients who develop thrombosis and are placed on anticoagulation while on this trial may continue on study at the discretion of the investigator)
- •The subject has had major surgery within 28 days of Study Day 1
- •The subject has had radiation therapy within 14 days of Study Day 1
- •The subject had prior bevacizumab within 28 days of study day 1
- •No prior treatment with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors; prior treatment with other investigational agents is allowed
- •The subject has a medical condition, which in the opinion of the study investigator, places them at unacceptably high risk for toxicities
- •Other active malignancy for which the patient has been treated within the past one year
- •Subjects with known human immunodeficiency virus (HIV) infection are excluded
- •Subject has documented left ventricular ejection fraction (LVEF) < 50%
- •Subject has Proteinuria > grade 1 at baseline measured by urine dipstick (2+ or greater) and confirmed by 24 hour (hr) urine collection (> = 1g/24hrs)
研究组 & 干预措施
Treatment (enzyme inhibitor)
Experimental
Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: linifanib (Drug)
结局指标
主要结局
Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15%
时间窗: Baseline and every 8 weeks, up to 2 years
Per Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Defined as the CR + PR recorded from the start of the treatment until disease progression/recurrence, the exact two-sided 95% confidence intervals will be reported.
次要结局
- Progression-free Survival(Every 3 months, up to 2 years)
- Overall Survival(Every 3 months, up to 2 years)
- Number of Patients With Each Worst-Grade Toxicity(date on-study up to 2 years following final dose of study)
研究者
Jordan Berlin, MD
Professor of Medicine; Clinical Director, GI Oncology Program; Director, Phase I Program; Medical Director, Clinical Trials Shared Resources; Medical Oncologist
Vanderbilt-Ingram Cancer Center
研究点 (2)
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