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

20 luglio 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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).

Tipo di studio

Interventistico

Iscrizione (Stimato)

30

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Olanda
      • Arnhem, Olanda
        • Non ancora reclutamento
        • Rijnstate
        • Contatto:
      • Arnhem, Olanda
      • Eindhoven, Olanda
      • Rotterdam, Olanda
        • Non ancora reclutamento
        • Erasmus Medical Centre
        • Contatto:
      • Utrecht, Olanda
        • Non ancora reclutamento
        • University Medical Centre Utrecht
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Previously irradiated, unresectable LRRC
Eligible for SBRT or CRT hyperfractionation
Radiazione: 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.
Radiazione: 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.
Sperimentale: Radiotherapy-naive, unresectable LRRC
Eligible for SIB
Radiazione: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer.
Lasso di tempo: 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.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Acute and late grade 3-5 radiation-induced toxicity per fractionation schedule
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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).

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Heike M.U. Peulen

Collaboratori

ZonMw: The Netherlands Organisation for Health Research and Development

Investigatori

  • Investigatore principale: H.M.U. Peulen, MD, PhD, Catharina Hospital, Department of Radiation Oncology

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 settembre 2026

Completamento primario (Stimato)

31 dicembre 2029

Completamento dello studio (Stimato)

31 dicembre 2031

Date di iscrizione allo studio

Primo inviato

30 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

20 luglio 2026

Primo Inserito (Effettivo)

22 luglio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

22 luglio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

20 luglio 2026

Ultimo verificato

1 luglio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Altri numeri di identificazione dello studio

  • NL-011150

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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