Multicentre, Prospective, Open-label Feasibility Study of Radiotherapy Dose Escalation for the Non-operative Management of Patients With Unresectable Locally Recurrent Rectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer.
研究概览
简要总结
The optimal curative-intent management of locally recurrent rectal cancer (LRRC) typically involves multimodality therapy, comprising neoadjuvant therapy and subsequent salvage surgery. However, in patients with unresectable LRRC, where surgical intervention is not feasible, management is limited to non-operative bimodality therapy with systemic therapy and radiotherapy. For this patient group, evidence guiding the optimisation of non-operative management remains limited, particularly regarding strategies to optimise radiotherapy and achieve durable control. In this context, the therapeutic goal is to achieve prolonged local control while minimising treatment-related toxicity. Radiotherapy dose escalation has been proposed as a potential strategy to achieve this balance. However, its feasibility and safety in the non-operative management of unresectable LRRC have not yet been established. As such, this study aims to evaluate the feasibility and safety of this radiotherapeutic approach, and to determine its impact on both symptomatic control and oncological outcomes.
详细描述
Objective: The primary objective of this study is to assess the feasibility of radiotherapy dose escalation in the non-operative treatment of previously irradiated and radiotherapy naïve patients with unresectable LRRC. Feasibility is defined as ≤7 participants with acute grade 3-5 radiation-induced toxicities (CTCAE version 5.0). Radiotherapy dose escalation is offered in a feasibility trial at a predefined dose level in two settings:
- (Chemo-)reirradiation: previously irradiated patients with unresectable LRRC undergo stereotactic body radiation therapy (SBRT) (daily adaptive magnetic resonance (MR) or cone beam computed tomography (CBCT)-guided) reirradiation (5 x 9 Gy) when feasible or, alternatively, hyperfractionated chemoreirradiation (50.4 Gy in 1.2 Gy BID fractions with concurrent capecitabine 825mg/m2 bidaily (BD)). SBRT feasibility is dependent on specific tumour criteria (i.e., <6 cm in tumour diameter, and tumour not infiltrating the lumen of the bowel- or bladder wall, as in accordance with the UK SABR consortium guidance(1)).
- Full-course chemoradiotherapy: radiotherapy naïve patients undergo full-course chemoradiotherapy with a simultaneous integrated boost (SIB; 25 × 2.6 Gy; EQD2Gy = 71 Gy, α/β = 5 Gy)(2) with concurrent capecitabine 825mg/m2 BD.
The investigators anticipate a safe toxicity profile, and potentially improved oncological outcomes. The secondary objectives are to determine symptomatic control, quality of life, local control, progression-free survival and overall survival.
Study design: This is a prospective, single-arm feasibility study. Eligible patients receive radiotherapy dose escalation at one predefined dose level in either a (chemo-)reirradiation or full-course radiotherapy setting.
Study population: A total of 30 patients will be included in the study. Eligible patients are divided in two treatment groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age ≥ 18 years old.
- •Diagnosis of locally recurrent rectal cancer, defined as recurrent disease within the pelvis after surgical excision for primary rectal or distal sigmoidal cancer, diagnosed either by histopathology or clinically proven (evidence on imaging in combination with clinical findings, with consensus in MDT). A second recurrence is eligible if (chemo-)reirradiation is considered feasible, with consensus in MDT.
- •Recurrent disease is determined as unresectable where surgery has been ruled out by clinicians (or refused by patient), with consensus in MDT.
- •Unresectable is defined as: expected gross incomplete resection with overt tumour remaining in the patient after resection, encasement of the ischiadic nerve and invasion of the cortex and/or neuroforamina from S2 and upwards.
- •- Either radiological absence of distant metastatic disease (M0), or, with (oligo)metastatic disease that does not require imminent start of systematic therapy at time of inclusion.
- •If systematic chemotherapy was previously administered prior to inclusion, and there is a current indication for local treatment with radiotherapy, patients are still eligible.
- •WHO/ECOG performance score 0-
- •MR pelvis and thoracoabdominal CT with interpretation no longer than 6 weeks prior to inclusion.
- •Written informed consent according to the ICH-GCP and national/local regulations.
排除标准
- •Radiological evidence of extensive metastatic disease (e.g., extensive liver or lung metastases) at time of inclusion, that requires imminent start of systemic therapy, with consensus in MDT.
- •Radiotherapy in the past 6 months.
- •Any contraindication for planned radiotherapy dose escalation, as determined by the radiation oncologist (e.g., residual grade 3 toxicity from previous radiotherapy).
- •Administration of bevacizumab/panitumumab/cetuximab <6 weeks prior to start radiotherapy dose escalation.
- •Severe active morbidity, concomitant disease or active infections.
- •dMMR/MSI status
结局指标
主要结局
To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer.
时间窗: During radiotherapy treatment and up to 3 months after completion of radiotherapy.
Outcome measure: the number of subjects with acute grade 3-5 radiation-induced toxicity (\<3 months), according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Feasibility-maximum: defined as ≤7 participants with acute grade 3-5 radiation-induced toxicity (\<3 months), according to CTCAE, version 5.0.
次要结局
- Acute and late grade 3-5 radiation-induced toxicity per fractionation schedule(During radiotherapy treatment, up to 3 months after completion of radiotherapy (acute toxicity), and from >3 months through 36 months after completion of radiotherapy (late toxicity).)
- Patient-reported quality of life and duration of symptomatic control(Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.)
- Infield progression-free survival(1, 2- and 3-years after the start of radiotherapy treatment.)
- Outfield progression-free survival(1, 2- and 3-years after the start of radiotherapy treatment.)
- Progression-free survival(1, 2- and 3-years after the start of radiotherapy treatment.)
- Disease-free survival(1, 2- and 3-years after the start of radiotherapy treatment.)
- Overall survival(1-, 2- and 3-year after study inclusion.)
- Compliance of treatment with radiotherapy dose escalation(From the start of radiotherapy through completion of radiotherapy (approximately 2-5 weeks depending on treatment arm).)
研究者
Heike M.U. Peulen
Dr. H.M.U. Peulen (Principal Investigator, Radiation Oncologist)
Catharina Ziekenhuis Eindhoven