Phase I Study of Pre-operative Capecitabine and Lenvatinib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This research study is designed to see if Capecitabine and Lenvatinib in combination with external radiation therapy are effective in treating locally advanced rectal adenocarcinoma in patients who have not yet had surgery, and what the best dosage is.
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 (archival tissue) confirmed adenocarcinoma of the rectum that begins within 12 cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy with no evidence of distant metastasis.
- •Locally advanced rectal cancer determined by any of the following features: 1.) Fixed or immobile tumor on physical exam and/or; 2.) T3 disease with invasion through the muscularis propria as defined by transrectal ultrasound, CT or MRI; 3.) T4 disease with invasion of adjacent structures such as pelvic sidewall, sacrum, pelvis, bladder and/or prostate as determined appropriate imaging modalities such as ultrasound, CT or MRI; 4.) Any T with + N on CT scan/MRI or transrectal ultrasound.
- •Age equal to or greater than 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
- •Adequate bone marrow, liver and renal function.
- •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
- •Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least 3 months after the last administration of lenvatinib.
- •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.
排除标准
- •Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Participants must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- •Previous pelvic irradiation therapy.
- •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- •Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- •Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
- •Active clinically serious infection > CTCAE Grade
- •Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic, attacks, deep vein thrombosis (DVT) within the past 6 months.
- •Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. (Treatment with low molecular weight heparin (LMWH) is allowed).
- •Active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated non-pelvic cancer from which the patient has been continuously disease free more than 3 years.
- •Marked baseline prolongation of QT/QTc interval (QTc interval ≥ 500 msec) using the Fridericia method (QTc = QT/RR0.33) for QTc analysis.
- •Greater than 30 mg/dL on urine analysis. Patients with >30 mg/dL on urine analysis on urine analysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Patients with 24-hour protein ≥1 g/24 hours will be ineligible.
- •Needing medical attention for serious bleeding in past 4 weeks.
- •Previous chemotherapy except for antiangiogenic agent or tyrosine kinase inhibitor (TKI) will be allowed as long as it is more than 5 years.
- •Major surgeries within 3 weeks of starting chemotherapy.
- •Evidence or history of bleeding diathesis.
- •Use of St. John's Wort or rifampin.
- •Known or suspected allergy to lenvatinib or any agent given in the course of this trial.
- •Any condition that impairs participant's ability to swallow whole pills.
- •Any malabsorption problem.
- •Medical need for the continued use of potent inhibitors/inducers of CYP3A
- •Creatinine clearance not within study guidelines.
研究组 & 干预措施
Pre-Surgery Chemotherapy/Radiotherapy
Pre-surgery chemotherapy and external radiation therapy. Dose escalation of Lenvatinib; fixed dose Capecitabine; Radiotherapy. Lenvatinib and capecitabine will be started on day 1 with radiation and will be discontinued on the last day of radiation. Surgical resection should occur between 6 - 10 weeks after the participant completes preoperative lenvatinib, capecitabine, and radiation therapy. Postoperative chemotherapy after surgery will be given at investigator's discretion.
干预措施: Lenvatinib (Drug)
Pre-Surgery Chemotherapy/Radiotherapy
Pre-surgery chemotherapy and external radiation therapy. Dose escalation of Lenvatinib; fixed dose Capecitabine; Radiotherapy. Lenvatinib and capecitabine will be started on day 1 with radiation and will be discontinued on the last day of radiation. Surgical resection should occur between 6 - 10 weeks after the participant completes preoperative lenvatinib, capecitabine, and radiation therapy. Postoperative chemotherapy after surgery will be given at investigator's discretion.
干预措施: Capecitabine (Drug)
Pre-Surgery Chemotherapy/Radiotherapy
Pre-surgery chemotherapy and external radiation therapy. Dose escalation of Lenvatinib; fixed dose Capecitabine; Radiotherapy. Lenvatinib and capecitabine will be started on day 1 with radiation and will be discontinued on the last day of radiation. Surgical resection should occur between 6 - 10 weeks after the participant completes preoperative lenvatinib, capecitabine, and radiation therapy. Postoperative chemotherapy after surgery will be given at investigator's discretion.
干预措施: External Radiation Therapy (XRT) (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Up to 6 months
MTD of lenvatinib used in combination with capecitabine and external beam radiation as neoadjuvant therapy for patients with locally advanced rectal carcinoma. The MTD of lenvatinib will be defined as the highest dose level at which no more than 1 out of 6 participants experiences dose-limiting toxicity (DLT). DLT: Any of the hematology or non-hematologic toxicities noted in Table 3 of the protocol, considered to be at least possibly related to lenvatinib and/or capecitabine.
次要结局
- Rate of Pathologic Response(Up to 36 months)
- Occurrence of Treatment Related Adverse Events(Up to 36 months)