Locally Recurrent Rectal CancerSTEP-UPNCT07721181
Radiotherapy Dose Escalation for Non-operative Management of Unresectable Locally Recurrent Rectal Cancer (STEP-UP)
A study testing SBRT, Hyperfractionated chemo-reirradiation and Full-course chemoradiotherapy in people with Locally Recurrent Rectal Cancer, run by Heike M.U. Peulen at 6 sites in Netherlands.
Trial summary
The optimal curative-intent management of locally recurrent rectal cancer (LRRC) typically involves multimodality therapy, comprising neoadjuvant therapy and subsequent salvage surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Recurrent Rectal Cancer
- What is being tested?
- SBRT, Hyperfractionated chemo-reirradiation and Full-course chemoradiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesNetherlands
- Study dates
- 24 Aug 2026to 31 Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Netherlands6 sites, 6 recruiting
- Recruiting
Radiotherapiegroep
Arnhem
M.D. den Hartogh, MD, PhD, 088-779 00 00 ext. +31, m.denhartogh@radiotherapiegroep.nl
- Recruiting
Rijnstate
Arnhem
I.M. Werter, MD, PhD, 088 - 005 8888 ext. +31, iwerter@rijnstate.nl
- Recruiting
Catharina Hospital
Eindhoven
H.M.U. Peulen, MD, PhD, 040 - 239 64 00 ext. +31, heike.peulen@catharinaziekenhuis.nl
- Not yet recruiting
MAASTRO Clinic
Maastricht, Limburg, 6229 ET
M. Berbée, MD, PhD, +31 088 445 5600, maaike.berbee@maastro.nl
- Not yet recruiting
Erasmus Medical Centre
Rotterdam
C.S.E.W. Schuurhuizen, MD, PhD, (010) 704 02 53 ext. +31, c.schuurhuizen@erasmusmc.nl
- Recruiting
University Medical Centre Utrecht
Utrecht
M.P.W. Intven, MD, PhD, 088 - 75 588 00 ext. +31, m.intven@umcutrecht.nl
About this study
Official title: 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.
Read the detailed description
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:
- (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.
- 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:
- (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.
- 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).
- Conditions
- Locally Recurrent Rectal Cancer
- Being tested
- SBRT, Hyperfractionated chemo-reirradiation, Full-course chemoradiotherapy
- Keywords
- Radiotherapy Dose Escalation, Non-Operative Management, Unresectable Locally Recurrent Rectal Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
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.
Hyperfractionated chemo-reirradiationRadiation
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.
Full-course chemoradiotherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Previously irradiated, unresectable LRRC | Experimental | Eligible for SBRT or CRT hyperfractionation Receives: Radiation: SBRT; Radiation: Hyperfractionated chemo-reirradiation |
| Radiotherapy-naive, unresectable LRRC | Experimental | Eligible for SIB Receives: Radiation: Full-course chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer.
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.
Measured: During radiotherapy treatment and up to 3 months after completion of radiotherapy.
Secondary outcomes (10)
Acute and late grade 3-5 radiation-induced toxicity per fractionation schedule
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
Infield progression-free survival
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).
Measured: 1, 2- and 3-years after the start of radiotherapy treatment.
Outfield progression-free survival
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).
Measured: 1, 2- and 3-years after the start of radiotherapy treatment.
Progression-free survival
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.
Measured: 1, 2- and 3-years after the start of radiotherapy treatment.
Disease-free survival
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.
Measured: 1, 2- and 3-years after the start of radiotherapy treatment.
Overall survival
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.
Measured: 1-, 2- and 3-year after study inclusion.
Compliance of treatment with radiotherapy dose escalation
Information on the completion of radiotherapy dose escalation is registered by the treating radiation oncologist.
Measured: From the start of radiotherapy through completion of radiotherapy (approximately 2-5 weeks depending on treatment arm).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2026
- Study start24 Aug 2026
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Recurrent Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Multicentre, Prospective, Open-Label Feasibility Study
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heike M.U. Peulen
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor-investigator, Heike M.U. Peulen, Catharina Ziekenhuis Eindhoven
- Investigators
- H.M.U. Peulen, MD, PhD, Principal investigator, Catharina Hospital, Department of Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07721181
- Sponsor's protocol ID
- NL-011150
- Acronym
- STEP-UP
- Status last verified
- Oct 2026
- First submitted
- 30 Jun 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Vande Kerckhove FEC, Beeftink JL, Tijssen RHN, Zijlstra J, Verrijssen AE, van Kuijk SMJ, van Ravensteijn SG, van Hellemond IEG, Calon TGA, Werter IM, Couwenberg AM, Schuurhuizen CSEW, den Hartogh MD, Hendriksen EM, Hupkens B, Buijsen J, Berbee M, Intven MPW, Bloemen JG, Nederend J, Burger JWA, Peulen HMU. Radiotherapy dose escalation for the non-operative management of patients with unresectable locally recurrent rectal cancer (STEP-UP): Study protocol for a multicentre, prospective, open-label feasibility study. Clin Transl Radiat Oncol. 2026 Oct 15;62:101326. doi: 10.1016/j.ctro.2026.101326. eCollection 2027 Jan.
PubMed 42927245
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Prospective, Open-label Feasibility Study of Radiotherapy Dose Escalation for the Non-operative Management of Patients With Unresectable Locally Recurrent Rectal Cancer
- ClinicalTrials.gov ID
- NCT07721181
- Acronym / sponsor ID
- STEP-UP / NL-011150
- Conditions
- Locally Recurrent Rectal Cancer
- Keywords
- Radiotherapy Dose Escalation, Non-Operative Management, Unresectable Locally Recurrent Rectal Cancer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Heike M.U. PeulenUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 24 Aug 2026 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 22 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- (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.
- 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:
- (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.
- 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicentre, Prospective, Open-Label Feasibility Study
| Arm | Type | Receives |
|---|---|---|
| Previously irradiated, unresectable LRRC | Experimental | Radiation: SBRT, Radiation: Hyperfractionated chemo-reirradiationEligible for SBRT or CRT hyperfractionation |
| Radiotherapy-naive, unresectable LRRC | Experimental | Radiation: Full-course chemoradiotherapyEligible for SIB |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRTSBRT (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. | Radiation | Previously irradiated, unresectable LRRC |
| Hyperfractionated chemo-reirradiationHyperfractionated 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. | Radiation | Previously irradiated, unresectable LRRC |
| Full-course chemoradiotherapyFull-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. | Radiation | Radiotherapy-naive, unresectable LRRC |
Primary outcome
To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer.
Time frame: 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.
10 secondary outcomes
Acute and late grade 3-5 radiation-induced toxicity per fractionation schedule
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline (at inclusion, before start of radiotherapy) and at 3, 6, 12, 24, and 36 months after completion of radiotherapy.
Infield progression-free survival
Time frame: 1, 2- and 3-years after the start of radiotherapy treatment.
Outfield progression-free survival
Time frame: 1, 2- and 3-years after the start of radiotherapy treatment.
Progression-free survival
Time frame: 1, 2- and 3-years after the start of radiotherapy treatment.
Disease-free survival
Time frame: 1, 2- and 3-years after the start of radiotherapy treatment.
Overall survival
Time frame: 1-, 2- and 3-year after study inclusion.
Compliance of treatment with radiotherapy dose escalation
Time frame: From the start of radiotherapy through completion of radiotherapy (approximately 2-5 weeks depending on treatment arm).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Derived from this study: PubMed 42927245Vande Kerckhove FEC, Beeftink JL, Tijssen RHN, Zijlstra J, Verrijssen AE, van Kuijk SMJ, van Ravensteijn SG, van Hellemond IEG, Calon TGA, Werter IM, Couwenberg AM, Schuurhuizen CSEW, den Hartogh MD, Hendriksen EM, Hupkens B, Buijsen J, Berbee M, Intven MPW, Bloemen JG, Nederend J, Burger JWA, Peulen HMU. Radiotherapy dose escalation for the non-operative management of patients with unresectable locally recurrent rectal cancer (STEP-UP): Study protocol for a multicentre, prospective, open-label feasibility study. Clin Transl Radiat Oncol. 2026 Oct 15;62:101326. doi: 10.1016/j.ctro.2026.101326. eCollection 2027 Jan.
- Individual participant dataSharing planned: Yes
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Relationship Between Quality of Life, Treatment Modalities, and Patient Treatment/Outcome Expectations
Rectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
H.M.U. Peulen, MD, PhD principal investigator
Catharina Hospital, Department of Radiation Oncology
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SBRT, Hyperfractionated chemo-reirradiation and Full-course chemoradiotherapy in people with Locally Recurrent Rectal Cancer, run by Heike M.U. Peulen at 6 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact H.M.U. Peulen, MD, PhD (040 - 239 64 00 ext. +31, heike.peulen@catharinaziekenhuis.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the feasibility of radiotherapy dose-escalation in the non-operative management of patients with unresectable locally recurrent rectal cancer. (time frame: During radiotherapy treatment and up to 3 months after completion of radiotherapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07721181, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.