Higher Radiation Dose to the Tumor May Help Avoid Surgery in Rectal Cancer Patients (REBOOT)
REctal Organ Preservation With a BOost Approach Using CBCT-based Online Adaptive radioTherapy
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Rationale:
Organ preservation has emerged as a promising alternative to total mesorectal excision (TME) for non-locally advanced rectal cancer, aiming to reduce long-term functional impairments and improve quality of life. While magnetic resonance (MR)-guided radiotherapy boosts have shown potential in enhancing organ preservation rates, their high costs, prolonged treatment times and limited accessibility prevent widespread adoption. To address this gap in current treatment options, this study investigates a more accessible online adaptive boost strategy based on cone-beam computed tomography (CBCT) imaging, with the aim of expanding organ-preserving treatment options for rectal cancer patients.
Objective:
The primary objective of this study is to evaluate the organ preservation rate at two-year follow-up in patients with non-locally advanced rectal cancer. Secondary objectives include the assessment of clinical and pathological response rates, recurrence and survival outcomes, biological effects, treatment-related toxicities, bowel function, quality of life, tumor regression, CBCT-based workflow, and target and organ motion during treatment.
Study design:
This study is designed as a non-randomized, single arm, monocenter, phase II clinical trial.
Study population:
Patients (n=25) older than 18 years with non-locally advanced rectal cancer (defined as cT1-3N0-IM0) and a wish for organ preservation, who are referred for treatment.
Intervention (if applicable):
Addition of a simultaneous integrated boost (SIB) to the standard chemoradiotherapy (CRT) scheme of 2.0 Gy to the mesorectum. The radiotherapy scheme consists of 25 fractions, delivering 2.0 Gy per fraction to the mesorectum and 2.4 Gy per fraction to the tumor and positive mesorectal lymph nodes.
Main study parameters/endpoints:
This study aims to demonstrate that the investigated treatment approach results in an increased organ preservation rate of 70% at two year follow-up compared to historical data.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Preclinical data confirmed the feasibility of the investigated SIB-CRT approach, demonstrating limited and clinically acceptable increases in organ at risk doses compared to the standard CRT scheme, all remaining well within clinical constraints. Furthermore, current literature supports the safety of dose escalation CRT strategies for rectal cancer, reporting manageable acute toxicity profiles, with symptoms typically returning to baseline after treatment. Based on these data, the investigated SIB-CRT strategy is expected to result in only minimal additional toxicities compared to standard CRT therapy.
The additional burden for the participants includes five MRI scans (approximately five hours total), scheduled alongside routine visits to minimize inconvenience. Patients will also be asked to complete three questionnaires at five time points, requiring approximately two hours in total, and to provide one additional 20 mL blood sample during three routine blood withdrawals.
The principal investigators consider the additional potential risk and burden for patients in the study to be acceptable. This study aims to significantly improve organ preservation rates, offering a meaningful benefit to individual patients by potentially avoiding TME surgery.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
-
-
South Holland
-
Rotterdam, South Holland, Holanda, 3015 GD
- Recrutamento
- Erasmus MC
-
Contato:
- Judith Sluijter, MSc
- Número de telefone: +31107035792
- E-mail: j.sluijter@erasmusmc.nl
-
Investigador principal:
- Claudia Schuurhuizen, PhD, MD
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Age ≥18 years
- Eastern cooperative oncology group (ECOG) performance status ≤2
- Histologically confirmed rectal adenocarcinoma
- Non-locally advanced rectal cancer, defined as (magnetic resonance imaging (MRI)-based) T1-3, N0/N1 (≤3 positive mesorectal lymph nodes), MX/M0
- Indication for curative treatment with organ preservation
- Discussed in the multidisciplinary tumor board (MTB)
- Written informed consent
Exclusion Criteria:
- Previous radiotherapy in the pelvic area
- Other malignancies, except for adequately treated basal cell carcinoma (BCC), at time of inclusion or within 3 years prior to inclusion
- Contra-indications for (chemo)radiotherapy or surgery
- Presence of lateral lymph nodes, cN2 status, extramural vascular invasion (EMVI) or mesorectal fascia involvement as seen on MRI
- Mucinous defined tumor on MRI
- Prior local excision of the primary tumor
- DPD (dihydropyrimidine dehydrogenase) deficiency
- Unable to understand the requirements of the study and to give written informed consent, as determined by the treating physician
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Simultaneous integrated boost
Treatment arm, in which all participating patients will receive the simultaneous integrated boost (SIB)
|
Addition of a simultaneous integrated boost (SIB) to the standard chemoradiotherapy (CRT) scheme of 2.0 Gy to the mesorectum.
The radiotherapy scheme consists of 25 fractions, delivering 2.0 Gy per fraction to the mesorectum and 2.4 Gy per fraction to the tumor and positive mesorectal lymph nodes.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Organ preservation
Prazo: During two-year follow-up
|
Organ preservation is considered unsuccessful if the rectum is surgically removed, a stoma is present, or a non-salvageable locoregional cancer recurrence is developed.
|
During two-year follow-up
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Rate of clinical complete response
Prazo: Assessed at the two response assessments (14-16 weeks and 26 weeks after the start of treatment)
|
Defined as the proportion of patients showing complete resolution of the tumor, assessed through endoscopy and MRI
|
Assessed at the two response assessments (14-16 weeks and 26 weeks after the start of treatment)
|
|
Rate of pathological complete response
Prazo: During two-year follow-up
|
Evaluated in patients undergoing surgical resection who did not achieve cCR.
pCR is defined as the absence of any residual tumor in surgical specimens, assessed via histopathological examination.
|
During two-year follow-up
|
|
Local progression-free survival
Prazo: During two-year follow-up
|
Defined as the absence of tumor regrowth at or near the primary tumor site.
Assessed through clinical evaluation and radiological imaging during the follow-up period.
|
During two-year follow-up
|
|
Distant progression-free survival
Prazo: During three-year follow-up
|
Defined as the absence of distant metastasis or death from any cause.
Monitored with regular imaging and clinical evaluations during the follow-up period.
|
During three-year follow-up
|
|
Overall survival
Prazo: During three-year follow-up
|
Defined as the time from the start of treatment to death from any cause.
|
During three-year follow-up
|
|
Biological effect of the treatment
Prazo: An additional 20 mL blood sample will be collected during scheduled blood withdrawal moments at three time points: (1) at baseline, (2) 2 weeks after start of treatment, and (3) 14-16 weeks after start of treatment.
|
Blood analyses to assess circulating tumor DNA (ctDNA) as a potential biomarker to predict treatment response.
|
An additional 20 mL blood sample will be collected during scheduled blood withdrawal moments at three time points: (1) at baseline, (2) 2 weeks after start of treatment, and (3) 14-16 weeks after start of treatment.
|
|
Toxicities
Prazo: During two-year follow-up
|
Acute and late toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.
Both patient- and clinician-reported toxicity will be assessed during regular follow-up visits.
Toxicities will be scored using the CTCAE scale, which ranges from Grade 0 (no toxicity) to Grade 5 (death), with higher grades indicating more severe adverse outcomes.
|
During two-year follow-up
|
|
Bowel function
Prazo: Baseline and 3, 6, 12 and 24 months after start of treatment
|
Evaluated using the low anterior resection syndrome (LARS) score, completed by the patient through a self-administered questionnaire.
by a questionnaire which the patient fills in by themself.
The total score ranges from 0 to 42 points, with higher scores indicating more severe symptoms.
The following categories are used: 0-20 points: No LARS, 21-29 points: Minor LARS, 30-42 points: Major LARS
|
Baseline and 3, 6, 12 and 24 months after start of treatment
|
|
Quality of Life (QoL)
Prazo: Baseline and 3, 6, 12 and 24 months after start of treatment
|
Measured using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire, filled in by the patient.
All of the scales and single-item measures range in score from 0 to 100.
A high score for the functional scale and functional single-items represents a high or healthy level of functioning.
A high score for the global health status/QoL scale represents a high QoL, whereas a high score for the symptom scale and single items represents a high level of symptomatology or problems.
|
Baseline and 3, 6, 12 and 24 months after start of treatment
|
|
Quality of Life (QoL)
Prazo: Baseline and 3, 6, 12 and 24 months after start of treatment
|
Measured using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CR29 questionnaire, filled in by the patient.
All of the scales and single-item measures range in score from 0 to 100.
A high score for the functional scale and functional single-items represents a high or healthy level of functioning, whereas a high score for the symptom scales and single-items represents a high level of symptomatology or problems.
|
Baseline and 3, 6, 12 and 24 months after start of treatment
|
|
Tumor regression during treatment, monitored through weekly MRI scans
Prazo: Baseline, and treatment week 2, 3, 4 and 5
|
Weekly information to evaluate tumor regression during treatment.
This includes five MRI scans in total, each requiring approximately one hour, including waiting time.
Retrospectively, these scans will also be used to assess inter- and intrafractional motion of the target and OARs to investigate the potential for further margin reduction.
|
Baseline, and treatment week 2, 3, 4 and 5
|
|
Target and organ intra- and interfraction motion
Prazo: CBCT data is gathered daily as standard-of-care during the 5-week treatment
|
Daily CBCT scans acquired pre-, intra-, and post-treatment will be retrospectively analyzed to assess inter- and intrafractional motion of the target and OARs to investigate the potential for further margin reduction in millimeters.
|
CBCT data is gathered daily as standard-of-care during the 5-week treatment
|
|
Feasibility of the CBCT-based SIB online adaptive workflow
Prazo: During the 5-week treatment course
|
Feasibility of the CBCT-based SIB online adaptive workflow including treatment time in minutes will be evaluated using treatment logs.
|
During the 5-week treatment course
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- NL-010517
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
produto fabricado e exportado dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .