A Phase I/II Study of Bevacizumab, Erlotinib and 5-fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy
研究概览
简要总结
The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients with locally advanced rectal cancer.
详细描述
- All participants will receive the following drugs: 5-fluorouracil (5-FU) given as a continuous 24-hour infusion; Bevacizumab given intravenously; erlotinib given orally at home. In the Phase I portion, we are looking for the highest dose of erlotinib that can be given safely in combination with the 5-FU, bevacizumab and radiation therapy. Therefore the dose of erlotinib may not be the same for each participant. The dose will increase until we find the highest dose without causing serious or unmanageable side effects.
- Study treatment is given as an outpatient and consists of 14 day cycles with a total of 3 cycles. Patients will be given all three study drugs and radiation therapy on a monday (unless a monday falls on on a holiday). This will be day 1 of the first treatment cycle. 5-FU is given continuously days 1-14. Bevacizumab is given on day 1. Erlotinib will be given on days 1-14. Radiation therapy will be performed on Days 1-5 and 8-12.
- The following tests and procedures will be performed weekly while participants are receiving study treatment: physical examination, measurement of vital signs, height and weight; performance status; blood work, urine sample.
- At the end of treatment the following tests will be performed: physical examination and measurement of vital signs; performance status; blood work; CT scans of chest, abdomen and pelvis. Patients will also be evaluated for surgery at this time. Patients will be followed every three months for the first three years after surgery, then every 6 months for the next two years.
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 primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy
- •Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI
- •ECOG performance status of 0-2
- •18 years of age or older
- •Creatinine of < 2.0
- •Adequate hepatic function
- •Adequate hematopoietic function
- •Use of effective means of contraception in subjects of child-bearing potential
排除标准
- •Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam
- •Prior chemotherapy or radiation therapy for treatment of colorectal cancer
- •Prior treatment with 5-FU
- •Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor
- •Patients must not be receiving any other investigational agent
- •Prior malignancy within the last 5 years except for completely excised skin cancer, in situ cervical cancer
- •Warfarin anticoagulation
- •Co-existent malignant disease
- •Current or recent participation in a clinical trial (within 4 weeks from the first day of treatment)
- •Pregnancy
- •Blood pressure of >150/100 mmHg
- •Unstable angina
- •NYHA Grade II or greater congestive heart failure
- •History of myocardial infarction within 6 months
- •History of stroke within 6 months
- •Clinically significant peripheral vascular disease
- •Evidence of bleeding diathesis or coagulopathy
- •Presence of central nervous system or brain metastases
- •Major surgical procedure, open biopsy, or significant trauma injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study
- •Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
- •Pregnant or lactating
- •Urine protein:creatinine ratio > or equal to one at screening
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0]
- •Serious, non-healing wound, ulcer, or bone fracture
研究组 & 干预措施
Chemotherapy and radiation
Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation.
干预措施: 5-fluorouracil (Drug)
Chemotherapy and radiation
Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation.
干预措施: bevacizumab (Drug)
Chemotherapy and radiation
Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation.
干预措施: erlotinib (Drug)
Chemotherapy and radiation
Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation.
干预措施: External beam radiation therapy (EBRT) (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy
时间窗: 3 years
MTD of Erlotinib was determined using a traditional 3 + 3 dose escalation scheme of three dose levels (50,100,150mg). Successive cohorts of 3-6 patients were enrolled into dose escalation cohorts for 14 day cycles. MTD reflects the highest dose of Erlotinib that had ≤1 out of 6 patients with Dose-Limiting Toxicity (DLT) at the highest dose level below the maximally administered dose. The maximally administered dose is the first dose that causes DLT in \>33% of patients. DLT was defined as: Any grade 4 neutropenia, Any grade 3 thrombocytopenia, or Any ≥ grade 3 non-hematologic toxicity that results in greater than 7 days interruption in therapy.
次要结局
- Summary of Grade 3 or Greater Toxicity(3 years)
- Percentage of Participants With Disease-free Survival(1, 2, 3 years)
- Post-operative Complications After Resection of Rectal Cancers Following Preoperative 5-FU, Bevacizumab, Erlotinib, and External Beam Radiation Therapy.(3 years)
研究者
Lawrence S. Blaszkowsky, MD
Assistant Physician
Massachusetts General Hospital