Phase-1 Study of Escalated-dose Pelvic Radiation Therapy Using Intensity-Modulated Radiotherapy (IMRT) With Simultaneous Integrated Boost (SIB), in Combination With Xeloda, for Initially Metastatic, Low and Middle Rectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- maximum tolerated radiation dose (MTD) delivered by IMRT with SIB, in combination with oral capecitabine, for initially metastatic, low and middle rectal cancer after 4 induction cycles of mFolfox6 regimen.
研究概览
简要总结
In initially metastatic rectal carcinoma, a neo-adjuvant multi-drug chemotherapy is usually performed, followed by a pelvic chemoradiation. The surgical indications on both metastases and the pelvic site are then discussed: in the case where a complete (or near-complete) response (CR) of the rectal tumor is observed (10 to 40%), the local surgery may be omitted or poned ("wait-and-see") in a sphincter-sparing strategy, in order to minimize or avoid the surgical morbidity, to focus on metastatic disease by the continuation of chemotherapy, and to preserve a better quality of life. After 8 weeks of induction chemotherapy (mFolfox6 regimen, 4 cycles), the aim of our study is to optimize the chemoradiation step on the distal rectal tumor, thanks to Intensity-Modulated Radiotherapy (IMRT) with simultaneous integrated boost (SIB) (Phase-1 part of the study), concomitantly with oral capecitabine. According to a Fibonacci dose-escalation scheme, 3 radiation dose-levels are defined, up to the definition of the maximal tolerated dose (MTD), requiring the inclusion of a maximum of 20 patients. Further patients will be included at the recommended dose for phase-2 (RDP2) in a two-step phase-2 study, considering simultaneously as principal objective at 12 months, both the efficacy (local CR rate in the range of 10 to 25%) and the tolerance (pelvic radiation disease: grade 3-4 toxicities in the range of 30 to 10%). Overall 65 patients will be included in the phase-2 study at the RDP2 dose.
详细描述
The study population has metastatic rectal cancer. After obtaining informed consent and if they fulfil all of the criteria for inclusion, patients will be included.
After 8 weeks of induction chemotherapy with FOLFOX, patients perform an imaging assessment.
Then they are treated by radiotherapy with an oral Xeloda At the end of irradiation, patients realize on other Imaging assessment. Patients are then followed for 2 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
- •Metastatic distal rectal carcinoma (low and middle);
- •age >18 years
- •Estimated life expectancy greater than 3 months
- •PS: ECOG<2
- •Normal hematologic, renal and hepatic functions
- •Normal or only partially decreased DPD activity
- •Effective contraception in women and men of childbearing age
- •Social insurance.
- •Signed informed consent
排除标准
- •No previous treatment with pelvic radiotherapy or chemotherapy
- •Disorder precluding understanding of trial information or informed consent
- •No severe or uncontrolled disease (infection, VIH, HBs, diabetes mellitus)
- •No peripheral neuropathy > grade 2
- •No inflammatory disease or fructosemia
- •Diarrhea of grade > 2
- •Pregnancy, breastfeeding women
- •Patients already included in another therapeutic within a period of 30 days
- •Other malignancy treated within the last 5 years (except non-melanoma skin cancer)
- •Bilateral total hip prosthesis
- •Patient is willing and able to comply with the protocol for the duration of the study including all scheduled treatment, visits and examinations
研究组 & 干预措施
IMRT + oral chemotherapy
Radiotherapy = IMRT with SIB. The overall duration of irradiation is 5 to 7 weeks Chemotherapy = oral capecitabine. Chemotherapy is taken in concomitance as radiotherapy days
干预措施: IMRT + oral chemotherapy (Combination Product)
结局指标
主要结局
maximum tolerated radiation dose (MTD) delivered by IMRT with SIB, in combination with oral capecitabine, for initially metastatic, low and middle rectal cancer after 4 induction cycles of mFolfox6 regimen.
时间窗: 84 months
MTD = dose level -1 after at least 2 patients with DLT to upper level
次要结局
- The prognostic value of PET(108 months)
- Local Progression-free survival at 12 months,(12 months after inclusion)
- Toxicity profile of the chemoradiation step for NCI.CTC grade 3-4 local toxicities due to "Pelvic Radiation Disease"(84 months)
- Overall survival at 2 years(24 months after inclusion)
- The usefulness of surgery(12 months after the end of radiochemotherapy)
- To evaluate quality of Life(84 months)