Phase I/II Trial of Preoperative Radiotherapy With Concurrent Bevacizumab, Erlotinib and Capecitabine for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Maximal tolerated dose (MTD)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of bevacizumab (Avastin) and erlotinib hydrochloride (Tarceva) that can be given in combination with standard radiation therapy and capecitabine before surgery to patients with rectal cancer. The safety and effectiveness of this combination of therapies will also be studied.
The goal of this Phase I trial was to determine the maximal tolerated dose (MTD) of concurrent capecitabine, bevacizumab and erlotinib with preoperative radiation therapy (RT) for rectal cancer. The trial completed as Phase I without progressing to the Phase II portion.
详细描述
The Study Drugs:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
Erlotinib hydrochloride is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.
Capecitabine is designed to interfere with the growth of cancer cells.
Study Phases:
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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Patients must be >/= 18 years of age.
- •All patients must have histologically confirmed adenocarcinoma of the rectum with pathologic material reviewed by the Department of Pathology at MD Anderson Cancer Center (MDACC).
- •Patients must have clinical stage II-III (T3, T4 or node-positive) based on computed tomography (CT), magnetic resonance (MR) or endoscopic ultrasound criteria.
- •Patients must have no distant metastatic disease on chest, abdomen and pelvic CT scan performed with IV contrast. If the CT was performed outside of MDACC, the slice thickness must be </= 7.5 mm. Criteria for pathologic enlargement of lymph nodes is > 15 mm on short axis dimension.
- •The rectal tumor must be either palpable on digital rectal exam or the inferior edge of the tumor must be within 12 cm of the anal verge based on rigid proctoscopy.
- •Patients must have absolute neutrophil count (ANC) >/= 1500/L, platelets >/= 100,000/mm^3, total serum bilirubin less than 2.0 mg%, blood urea nitrogen (BUN) </= 30 mg%, creatinine </= 1.5 mg% and creatinine clearance >/= 30ml/min (estimated as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (estimated creatinine clearance 30-50 mL/min) at baseline, a dose reduction to 75% of the capecitabine starting dose is recommended.
- •Hemoglobin >/= 9 gm/dL (may be transfused to maintain or exceed this level).
- •Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary. Patients must be made aware of their other treatment options.
排除标准
- •Prior radiotherapy to the pelvis.
- •Any prior chemotherapy.
- •Prior vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR)-directed therapy, such as bevacizumab, cetuximab, erlotinib, or gefitinib.
- •Current, prior or planned participation in any other experimental drug study.
- •Pregnant or lactating woman. Woman of childbearing potential with either a positive or no pregnancy test at baseline. Women / men of childbearing potential not using a reliable contraceptive method (oral contraceptive, other hormonal contraceptive, intrauterine device, diaphragm or condom). (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 30 days from the date of the last study drug administration.
- •Serious, uncontrolled, concurrent infection(s) requiring intravenous (IV) antibiotics.
- •Treatment for other clinically significant cancers within the last five years, except cured non-melanoma skin cancer and treated in-situ cervical cancer.
- •Inadequately controlled hypertension [systolic blood pressure of >130 and/or diastolic blood pressure of >90 mmHg on antihypertensive medication at time of study entry and/or at time of starting therapy] history of myocardial infarction or unstable angina within 12 months prior to study enrollment, New York Heart Association Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible) or Class II or greater peripheral vascular disease
- •History of stroke or transient ischemic attack at any time,history of hypertensive crisis or hypertensive encephalopathy.
- •Aspartate aminotransferase or alanine aminotransferase (AST or ALT) >/= 2.5 times the upper limit of normal.
- •Inability to swallow oral medication.
- •Evidence of bleeding diathesis or coagulopathy, international normalized ratio (INR) >/= 2.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day
- •Proteinuria at baseline or clinically significant impairment of renal function as demonstrated by either a. Urine protein:creatinine ratio >/= 1.0 at screening. b. Urine dipstick for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
- •Current serious, nonhealing wound, ulcer, or bone fracture.
- •History of aortic aneurysm > 4.5 or aortic dissection.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day
- •Patients who have had an organ allograft.
- •Patients on Coumadin are recommended to be changed to Low Molecular Weight Heparin (LMWH) at least 1 week prior to starting capecitabine. If patients cannot be switched to LMWH, then extra monitoring of their International Normalized Ratio (INR) will be performed.
- •Patients taking Sorivudine or Brivudine must be off of these drugs for 4 weeks. Patients taking cimetidine must have this drug discontinued. Ranitidine or a drug from another anti-ulcer class can be substituted for cimetidine if necessary. If patient is currently receiving allopurinol, must discuss with PI to see of another agent may substitute for it.
- •Patients with known Gilberts disease will be considered ineligible due to potential UGTA1 polymorphism effects on metabolism for erlotinib.
- •Inability to comply with study and/or follow-up procedures.
- •Known hypersensitivity to any component of bevacizumab, erlotinib or capecitabine
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Peripheral arterial thrombosis within 6 months prior to study enrollment
研究组 & 干预措施
Bevacizumab + Erlotinib + Capecitabine + Radiation Therapy
Bevacizumab 5 mg/kg intravenous (IV) every 2 weeks for 3 Doses (Weeks 1, 3, 5). Erlotinib starting dose 50 mg orally daily Weeks 1-3. Capecitabine starting dose 650 mg/m^2 orally twice daily Monday-Friday for 6 Weeks. Radiation Therapy 30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments. At least 8 weeks after radiation therapy, surgical removal of rectal tumor.
干预措施: Bevacizumab (Drug)
Bevacizumab + Erlotinib + Capecitabine + Radiation Therapy
Bevacizumab 5 mg/kg intravenous (IV) every 2 weeks for 3 Doses (Weeks 1, 3, 5). Erlotinib starting dose 50 mg orally daily Weeks 1-3. Capecitabine starting dose 650 mg/m^2 orally twice daily Monday-Friday for 6 Weeks. Radiation Therapy 30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments. At least 8 weeks after radiation therapy, surgical removal of rectal tumor.
干预措施: Capecitabine (Drug)
Bevacizumab + Erlotinib + Capecitabine + Radiation Therapy
Bevacizumab 5 mg/kg intravenous (IV) every 2 weeks for 3 Doses (Weeks 1, 3, 5). Erlotinib starting dose 50 mg orally daily Weeks 1-3. Capecitabine starting dose 650 mg/m^2 orally twice daily Monday-Friday for 6 Weeks. Radiation Therapy 30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments. At least 8 weeks after radiation therapy, surgical removal of rectal tumor.
干预措施: Erlotinib (Drug)
Bevacizumab + Erlotinib + Capecitabine + Radiation Therapy
Bevacizumab 5 mg/kg intravenous (IV) every 2 weeks for 3 Doses (Weeks 1, 3, 5). Erlotinib starting dose 50 mg orally daily Weeks 1-3. Capecitabine starting dose 650 mg/m^2 orally twice daily Monday-Friday for 6 Weeks. Radiation Therapy 30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments. At least 8 weeks after radiation therapy, surgical removal of rectal tumor.
干预措施: Radiation Therapy (Radiation)
Bevacizumab + Erlotinib + Capecitabine + Radiation Therapy
Bevacizumab 5 mg/kg intravenous (IV) every 2 weeks for 3 Doses (Weeks 1, 3, 5). Erlotinib starting dose 50 mg orally daily Weeks 1-3. Capecitabine starting dose 650 mg/m^2 orally twice daily Monday-Friday for 6 Weeks. Radiation Therapy 30 minute radiation treatments, dose of 50.4 Gy once daily on 5 consecutive days, for up to 5 weeks and 3 days, totaling 28 treatments. At least 8 weeks after radiation therapy, surgical removal of rectal tumor.
干预措施: Surgery (Procedure)
结局指标
主要结局
Maximal tolerated dose (MTD)
时间窗: Continuoual Reassessment Weeks 1- 6
MTD derived from differing dose combinations of Capecitabine, Bevacizumab, and Erlotinib of using the continual reassessment method (CRM). Dose limiting toxicity defined as any grade 3 or higher acute toxicity during chemoradiation. The MTD will be defined as the dose at which grade 3 or higher acute toxicity exceeds 25%.
次要结局
未报告次要终点