Phase II Study of SIB-IMRT in Combination With 5-FU and Mitomycin-C Among Patients With Locally Advanced Anal Canal Cancer: Efficacy, Safety and Quality of Life
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 71
- 试验地点
- 11
- 主要终点
- Efficacy: The 3-month locoregional control rate
研究概览
简要总结
Anal canal carcinoma (ACC) represents 1.2% of digestive cancers. Its incidence is increasing. As epidermoid ACC (95% of ACC) are particularly sensitive to radio and chemotherapy, concomitant radio-chemotherapy is the standard treatment of locally advanced ACC, with proven efficacy on locoregional control, anal sphincter preservation, progression-free survival and complete response rate higher than 80%.
Nevertheless, conventional radiotherapy frequently induces significant non-haematological toxicities requiring treatment interruptions. Thus, treatment usually includes a chemotherapy (5-Fluorouracil and Mitomycine-C) and 25 fractions of 1.8 Gy followed by a planned 1-week (or more) interruption and a boost, for a total 54-60 Gy radiation dose over 9 weeks.
Considering the numerous anatomic pelvic structures, ACC has become a localisation of interest for Intensity-Modulated Radiation Therapy (IMRT) associated with less toxicity.
However, IMRT induces grade≥3 cutaneous toxicities requiring irradiation breaks. Dose escalade did not show its interest: 60 Grays remains the standard.
Assuming the deleterious effect of increased overall treatment time on local control and survival in head-and-neck and cervical cancers and the epidermoid histology of ACC, the benefit of no irradiation break on ACC tumour control is of interest.
IMRT offers the possibility to deliver different doses to different target volumes simultaneously by altered fractionation schedule like SIB-IMRT (simultaneously integrated boost-IMRT). Several SIB-IMRT schedules have been retrospectively evaluated. Similar results were observed with moderate doses and schedules delivering higher doses with short interruptions. Nevertheless, standard SIB-IMRT schedule in ACC still not exist.
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
- •WHO performance status ≤ 2
- •Age > 18 years
- •Epidermoid anal canal carcinoma histologically proven, locally advanced with an indication of radiation of pelvic and inguinal nodes concomitantly to chemotherapy
- •The T corresponds to the larger dimension of tumor at the rectal examination and the N is assessed by imaging pelvic MRI-imaging, CT-scan, optionally PET-CT). Eligible tumors are: T2 more than 4 cm N0-N3, T2-T4 N1-N3 or usN1, T3-T4 N0, M0 according to the 6th edition of the American Joint Committee on cancer staging manual.
- •Laboratory data obtained ≤ 14 days prior to registration on study, with adequate bone marrow, hepatic and renal function defined as follows: hemoglobinemia, neutrophil, platelet counts, bilirubin and creatinin level
- •Informed consent form
排除标准
- •Previous invasive cancer within 5 years except basocellular cancer and in situ cervical cancer
- •Tumors with predominant skin involvement
- •Presence of metastases
- •History of pelvic irradiation
- •Contraindication to radiotherapy or chemotherapy
- •Known HIV positive patients
研究组 & 干预措施
Concomitant chemotherapy and radiotherapy
Chemoradiotherapy with two cycles of 5FU and Mitomycin-C plus radiotherapy by SIB-IMRT (for simultaneous integrated boost intensity modulated radiation therapy) day 1 to day 50 in 36 fractions
干预措施: 5Fluorouracile and Mitomycin-C (Drug)
Concomitant chemotherapy and radiotherapy
Chemoradiotherapy with two cycles of 5FU and Mitomycin-C plus radiotherapy by SIB-IMRT (for simultaneous integrated boost intensity modulated radiation therapy) day 1 to day 50 in 36 fractions
干预措施: Simultaneously integrated boost of intensity modulated radiation therapy (SIB-IMRT) by tomotherapy (Radiation)
结局指标
主要结局
Efficacy: The 3-month locoregional control rate
时间窗: 3 months after the end of radiotherapy
The 3-month locoregional control rate after the end of IMRT by helical tomotherapy defined by the proportion of patients alive with no local disease progression 3 months after the end of radiotherapy
Tolerance profile: Proportion of patients with no significant toxicities responsible for irradiation breaks
时间窗: Until 11 weeks after treatment start
Tolerance profile: Proportion of patients with no significant (grade ≥3 according to NCI CTCAE v4.03) toxicities responsible for irradiation breaks
Efficacy: The 3-month Locoregional Control Rate
时间窗: 3 months after the end of radiotherapy
The 3-month locoregional control rate after the end of IMRT by helical tomotherapy defined by the proportion of patients alive with no local disease progression 3 months after the end of radiotherapy
Tolerance Profile: Proportion of Patients With no Significant Toxicities Responsible for Irradiation Breaks
时间窗: Until 11 weeks after treatment start
Tolerance profile: Proportion of patients with no significant (grade ≥3 according to NCI CTCAE v4.03) toxicities responsible for irradiation breaks
次要结局
- Quality of life measured by the EORTC QLQ-C30 (version 3.0)(From treatment start to 5 years after the end of radiotherapy)
- The acute and late toxicities assessed according to NCI CTCAE v4.03(From treatment start to 5 years after the end of radiotherapy)
- The 6- and 12-month locoregional control rates defined by the proportion of patients with no local disease progression at 6 and 12 months after the end of radiotherapy(at 6 and 12 months after the end of radiotherapy)
- Duration of response defined by the time elapsed from first objective response to progression or death from any cause(From months 3 to progression)
- Quality of life measured by the additional colorectal module QLQ-CR 29(From treatment start to 5 years after the end of radiotherapy)
- Quality of life measured by the Vaizey incontinence scale(From treatment start to 5 years after the end of radiotherapy)
- The acute and late toxicities assessed according the SOMA/LENT scale(From treatment start to 5 years after the end of radiotherapy)
- Duration of Response Defined by the Time Elapsed From First Objective Response to Progression or Death From Any Cause(From months 3 to progression)
- Quality of Life Measured by the EORTC QLQ-C30 (Version 3.0)(6 months after treatment start)
- The Acute and Late Toxicities Assessed According to NCI CTCAE v4.03(From treatment start to 24 months after the end of radiotherapy)
- The 6- and 12-month Locoregional Control Rates Defined by the Proportion of Patients With no Local Disease Progression at 6 and 12 Months After the End of Radiotherapy(at 6 and 12 months after the end of radiotherapy)
- Quality of Life Measured by the Additional Colorectal Module QLQ-CR 29(6 months after treatment start)
- Quality of Life Measured by the Vaizey Incontinence Scale(6 months after treatment start)
- The Acute Toxicities Assessed According the SOMA/LENT Scale(At 3 months after treatment initiation)