A Phase I Trial of Lenvatinib (Multi-kinase Inhibitor) and Capecitabine (Anti-metabolite) in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD) of Combination Treatment with Lenvatinib and Capecitabine in Advanced and/or Metastatic Cancer Refractory to Standard Treatment
研究概览
简要总结
There are 2 phases in this study: Phase 1 (dose escalation) and Phase 2 (dose expansion).
The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of lenvatinib and Xeloda (capecitabine) that can be given to patients with advanced cancer. The goal of Phase 2 of this study is to learn if the dose of lenvatinib and capecitabine found in Phase 1 can help to control advanced cancer.
The safety of this drug combination will be studied in both phases of the study.
详细描述
Study Groups:
If participant is are found to be eligible to take part in this study, they will be assigned to a study group based on when they join this study. Up to 4 groups of up to 18 participants will be enrolled in Phase 1 of the study, and up to 28 participants will be enrolled in Phase 2.
If participant is enrolled in Phase 1, the dose of lenvatinib they receive will depend on when they join this study. The first group of participants will receive the lowest dose level of lenvatinib. Each new group will receive a higher dose of lenvatinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of lenvatinib is found.
If participant is enrolled in Phase 2, they will receive lenvatinib at the highest dose that was tolerated in Phase 1.
All participants will receive the same dose of capecitabine.
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 with a histologically and/or cytologically confirmed solid tumor who are resistant / refractory to approved therapies or for whom no curative therapies are available.
- •All previous treatment (including surgery, radiotherapy and systemic anti-neoplastic therapy) must have been completed at least three weeks prior to study entry and any acute toxicities must have resolved.
- •Aged >/= 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of </=
- •Written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
- •Willing and able to comply with the protocol guidelines for the duration of the study.
排除标准
- •Unstable metastases to the central nervous system (CNS).
- •Any of the following laboratory parameters: a) hemoglobin < 9 g/dL (5.6 mmol/L); b) neutrophils <1.5 x 109/L; c) platelets <100 x 109/L; d) serum bilirubin >25 µmol/L (1.5 mg/dL); e) liver function tests with values >3 x upper limit of normal (ULN) f) serum creatinine >1.5 x ULN or creatinine clearance < 60 mL/minute
- •Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection
- •Centrally located non-small cell lung cancers and squamous cell lung cancers
- •Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start
- •Patients with marked Baseline prolongation of QT/QTc interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysis
- •Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants, such as warfarin. Occasional use of NSAIDs and antiplatelet agents such as aspirin, clopidogrel, aggrenox and dipyridamole are not considered exclusionary if taken <7 days per 28 days. However, if the patient requires chronic use (>/=7 days out of 28 days) of full doses of aspirin or NSAIDs then the patient is excluded.
- •Requirement for chronic use of full dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
- •Poorly controlled hypertension (defined as requiring changes in any hypertensive regimen within 1 week of study entry) or patients diagnosed with hypertension based on repeat blood pressure measurements of >160/90 mmHg at Screening
- •Proteinuria > 1+ on urine dipstick testing or 30 mg/dL
- •A history of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within four weeks of starting therapy or who have not recovered from major surgery within three weeks of starting therapy
- •History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance.
- •Any treatment with investigational drugs within 30 days before the start of the study
- •Previous treatment with E7080
- •Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
- •Fertile males with female partners who are not willing to use contraception or whose female partners are not using adequate contraceptive protection
- •Legal incapacity
研究组 & 干预措施
Lenvatinib + Capecitabine
Phase 1 Study Escalation: Group consists of participants with various solid tumors.
Dose of Lenvatinib received depends on when joining study. First group of participants receive lowest dose level of Lenvatinib. Each new group receives a higher dose of Lenvatinib than the group before it, if no intolerable side effects were seen. This continues until highest tolerable dose of Lenvatinib found.
All participants receive the same dose of Capecitabine.
Phase 2 Study Expansion: Group consists of participants with advanced breast cancer and any solid tumors with confirmed FGFR abnormalities.
Participants receive Lenvatinib at the highest dose that was tolerated in Dose Escalation Phase.
All participants receive the same dose of Capecitabine.
干预措施: Lenvatinib (Drug)
Lenvatinib + Capecitabine
Phase 1 Study Escalation: Group consists of participants with various solid tumors.
Dose of Lenvatinib received depends on when joining study. First group of participants receive lowest dose level of Lenvatinib. Each new group receives a higher dose of Lenvatinib than the group before it, if no intolerable side effects were seen. This continues until highest tolerable dose of Lenvatinib found.
All participants receive the same dose of Capecitabine.
Phase 2 Study Expansion: Group consists of participants with advanced breast cancer and any solid tumors with confirmed FGFR abnormalities.
Participants receive Lenvatinib at the highest dose that was tolerated in Dose Escalation Phase.
All participants receive the same dose of Capecitabine.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Combination Treatment with Lenvatinib and Capecitabine in Advanced and/or Metastatic Cancer Refractory to Standard Treatment
时间窗: 3 weeks
MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v4.0,
次要结局
- Antitumor Efficacy of Combination of Lenvatinib and Capecitabine in Breast Cancer and Solid Tumors with FGFR Abnormality(42 days)