このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

Radiotherapy Dose Escalation for Non-operative Management of Unresectable Locally Recurrent Rectal Cancer (STEP-UP) (STEP-UP)

2026年7月20日 更新者：Heike M.U. Peulen

Multicentre, Prospective, Open-label Feasibility Study of Radiotherapy Dose Escalation for the Non-operative Management of Patients With Unresectable Locally Recurrent Rectal Cancer

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.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

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:

  1. (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)).
  2. 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:

  1. (Chemo-)reirradiation: Previously irradiated patients with unresectable LRRC (without distant metastases, or, with (oligo)metastatic disease that does not require imminent start of systematic therapy) treated with non-operative management.
  2. Full-course chemoradiotherapy: Radiotherapy-naïve patients with unresectable LRRC (without distant metastases, or, with (oligo)metastatic disease that does not require imminent start of systematic therapy) treated with non-operative management.

Intervention study: All cases are reviewed in a multidisciplinary tumour board before enrolment. Interventions are defined as follows:

  1. (Chemo-)reirradiation: SBRT (daily adaptive MR or CBCT-guided) will be delivered when feasible, depending on tumour characteristics (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). The SBRT regimen consists of 5 fractions of 9 Gy. Alternatively, hyperfractionated chemo-reirradiation will be delivered, consisting of 50.4 Gy in 1.2 Gy twice-daily fractions (BID), in combination with concurrent capecitabine 825mg/m2 BD.
  2. Full-course chemoradiotherapy: delivered with a simultaneous integrated boost (SIB) technique (25x2.6 Gy), corresponding to an EQD2Gy (α/β = 5 Gy, rectum) of 71 Gy, with concurrent capecitabine 825mg/m2 BD.

Main study parameters/endpoints: The primary objective is to evaluate the feasibility of radiotherapy dose escalation, as defined by the incidence of acute (<3 months) grade 3-5 radiation-induced toxicities ≤7 participants (CTCAE version 5.0). Secondary objectives include acute and late radiation-induced toxicity stratified per fractionation schedule, quality of life and symptomatic control (using validated patient-reported outcome questionnaires), and 1- and 3- year (infield and outfield) progression-free survival (PFS), disease-free survival (DFS) and overall survival (OS).

研究の種類

介入

入学 (推定)

30

段階

  • 適用できない

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

  • オランダ
      • Arnhem、オランダ
        • まだ募集していません
        • Rijnstate
        • コンタクト：
      • Arnhem、オランダ
        • まだ募集していません
        • Radiotherapiegroep
        • コンタクト：
      • Eindhoven、オランダ
      • Rotterdam、オランダ
        • まだ募集していません
        • Erasmus Medical Centre
        • コンタクト：
      • Utrecht、オランダ
        • まだ募集していません
        • University Medical Centre Utrecht
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  • 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 0-2.
  • 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.

Exclusion Criteria:

  • 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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：非ランダム化
  • 介入モデル：順次割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：Previously irradiated, unresectable LRRC
Eligible for SBRT or CRT hyperfractionation
放射線：SBRT
SBRT (daily adaptive MR or CBCT-guided) will be delivered when feasible, depending on tumour characteristics (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). The SBRT regimen consists of 5 fractions of 9 Gy.
放射線：Hyperfractionated chemo-reirradiation
Hyperfractionated chemo-reirradiation will be delivered, consisting of 50.4 Gy in 1.2 Gy twice-daily fractions (BID), in combination with concurrent capecitabine 825mg/m2 BD.
実験的：Radiotherapy-naive, unresectable LRRC
Eligible for SIB
放射線：Full-course chemoradiotherapy
Full-course chemoradiotherapy: delivered with a simultaneous integrated boost (SIB) technique (25x2.6 Gy), corresponding to an EQD2Gy (α/β = 5 Gy, rectum) of 71 Gy, with concurrent capecitabine 825mg/m2 BD.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer.
時間枠：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.
During radiotherapy treatment and up to 3 months after completion of radiotherapy.

二次結果の測定

結果測定
メジャーの説明
時間枠
Acute and late grade 3-5 radiation-induced toxicity per fractionation schedule
時間枠：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).
To determine acute (<3 months) and late (presenting after 3 months up to 36 months) grade 3-5 radiation-induced toxicity , according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, stratified 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
時間枠：Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
To determine patient-reported quality of life and duration of symptomatic control following treatment with radiotherapy dose escalation. Generic and cancer-specific quality of life assessments are assessed with European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaires: QLQ-C30. The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
Patient-reported quality of life and duration of symptomatic control
時間枠：Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
To determine patient-reported quality of life and duration of symptomatic control following treatment with radiotherapy dose escalation. Generic and cancer-specific quality of life assessments are assessed with European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaires: QLQ-CR29. The QLQ-CR29 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
Patient-reported quality of life and duration of symptomatic control
時間枠：Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
To determine patient-reported quality of life and duration of symptomatic control following treatment with radiotherapy dose escalation. Generic and cancer-specific quality of life assessments are assessed with EuroQol Group 5-level EQ-5D (EQ-5D-5L), a 5 point scale. Higher scores corresponds with a higher level of symptoms on the symptom scale.
Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
Infield progression-free survival
時間枠：1, 2- and 3-years after the start of radiotherapy treatment.
To determine 1-, 2- and 3-year infield progression-free survival. Defined as the time interval from start of radiotherapy dose escalation to radiological or clinical confirmed infield progression (defined as recurrence or disease progression within the PTV).
1, 2- and 3-years after the start of radiotherapy treatment.
Outfield progression-free survival
時間枠：1, 2- and 3-years after the start of radiotherapy treatment.
To determine 1-, 2- and 3-year outfield progression-free survival. Defined as the time interval from start of radiotherapy dose escalation to radiological or clinical confirmed outfield progression (defined as recurrence or disease progression outside the PTV).
1, 2- and 3-years after the start of radiotherapy treatment.
Progression-free survival
時間枠：1, 2- and 3-years after the start of radiotherapy treatment.
To determine 1-, 2- and 3-year progression-free survival. Defined as the time interval from start of radiotherapy dose escalation to radiological or clinical confirmed locoregional progression. Progression is registered by the treating physician in the patient file during follow-up.
1, 2- and 3-years after the start of radiotherapy treatment.
Disease-free survival
時間枠：1, 2- and 3-years after the start of radiotherapy treatment.
To determine 1, 2-, and 3-year disease-free survival. Defined as the time interval from start of radiotherapy dose escalation to first documented sign of disease progression (including locoregional progression or distant metastases) or death from any course.
1, 2- and 3-years after the start of radiotherapy treatment.
Overall survival
時間枠：1-, 2- and 3-year after study inclusion.
To determine 1-, 2- and 3-year overall survival. Defined as the time interval from date of inclusion to date of death. Mortality is registered in the patient file which is linked to municipal personal records database.
1-, 2- and 3-year after study inclusion.
Compliance of treatment with radiotherapy dose escalation
時間枠：From the start of radiotherapy through completion of radiotherapy (approximately 2-5 weeks depending on treatment arm).
Information on the completion of radiotherapy dose escalation is registered by the treating radiation oncologist.
From the start of radiotherapy through completion of radiotherapy (approximately 2-5 weeks depending on treatment arm).

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Heike M.U. Peulen

協力者

ZonMw: The Netherlands Organisation for Health Research and Development

捜査官

  • 主任研究者：H.M.U. Peulen, MD, PhD、Catharina Hospital, Department of Radiation Oncology

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年9月1日

一次修了 (推定)

2029年12月31日

研究の完了 (推定)

2031年12月31日

試験登録日

最初に提出

2026年6月30日

QC基準を満たした最初の提出物

2026年7月20日

最初の投稿 (実際)

2026年7月22日

学習記録の更新

投稿された最後の更新 (実際)

2026年7月22日

QC基準を満たした最後の更新が送信されました

2026年7月20日

最終確認日

2026年7月1日

詳しくは

本研究に関する用語

キーワード

その他の研究ID番号

  • NL-011150

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

購読する