Hypofractionated Whole Pelvic Chemoradiotherapy With iRex Optimization in Cervical Cancer (HYPOCx-iRex)
HYPOfractionated Whole Pelvic Concurrent Chemoradiotherapy in Cervical (Cx) Cancer With "Indirect Excess Dose Volume Ratio (iRex)" - Optimized Image Guided Adaptive Brachytherapy (HYPOCx-iRex Trial) : A Phase II Non-inferiority Randomized Controlled Trial
This study is a randomized controlled trial designed to compare hypofractionated whole pelvic radiotherapy with conventional radiotherapy in patients with cervical cancer undergoing concurrent chemoradiotherapy.
Hypofractionated radiotherapy delivers a higher dose per treatment over a shorter overall treatment time, which may reduce the number of hospital visits and improve treatment convenience for patients. Conventional radiotherapy requires more treatment sessions over a longer period.
The purpose of this study is to evaluate whether hypofractionated radiotherapy is as safe and effective as conventional radiotherapy. The primary outcomes focus on treatment-related toxicity, while secondary outcomes include tumor response, survival outcomes, quality of life, and treatment-related factors.
In addition, this study will evaluate a novel planning approach called the indirect excess dose volume ratio (iRex) to optimize brachytherapy planning and potentially reduce radiation-related side effects.
Visão geral do estudo
Status
Condições
Descrição detalhada
Cervical cancer remains a significant global health burden, particularly in low- and middle-income countries. Standard treatment for locally advanced cervical cancer consists of conventional fractionated radiotherapy combined with concurrent chemotherapy, followed by brachytherapy. However, conventional radiotherapy requires prolonged treatment duration, which may negatively impact patient compliance, healthcare resource utilization, and treatment outcomes.
Hypofractionated radiotherapy delivers a higher dose per fraction while maintaining a comparable total biological dose, thereby reducing the overall treatment time. Shortening treatment duration may improve tumor control based on radiobiological principles and reduce patient burden, including travel and treatment-related costs.
Previous studies suggest that hypofractionated radiotherapy may provide comparable oncologic outcomes to conventional radiotherapy, with acceptable toxicity profiles. However, high-quality randomized evidence remains limited, particularly using modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) and image-guided adaptive brachytherapy (IGABT).
This study is a Phase II randomized controlled trial designed to evaluate the safety and feasibility of hypofractionated whole pelvic radiotherapy compared with conventional fractionation. Patients will be randomized to receive either hypofractionated or conventional external beam radiotherapy, both combined with concurrent chemotherapy and followed by brachytherapy.
In addition, this study incorporates a novel dosimetric parameter, the indirect excess dose volume ratio (iRex), to optimize brachytherapy planning. The use of iRex in combination with standard dose constraints may improve spatial dose control and reduce radiation-induced toxicity.
The primary objective is to assess treatment-related toxicity, while secondary objectives include tumor response, survival outcomes, quality of life, dosimetric parameters, and cost-effectiveness. This study aims to provide evidence supporting a shorter, more efficient radiotherapy regimen without compromising safety or efficacy.
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
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Bangkok
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Bangkok, Bangkok, Tailândia
- Siriraj Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Cancer of the uterine cervix considered suitable for curative treatment with definitive radio-(chemo)therapy including imaged-guided BT
- Positive biopsy showing squamous-cell carcinoma, adenocarcinoma, or adeno-squamous cell carcinoma of the uterine cervix
- Staging according to FIGO 2018 and TNM guidelines
- MRI of the pelvis at diagnosis is performed
- MRI, CT, or PET-CT of the retroperitoneal space and abdomen at diagnosis is performed
- MRI with the applicator in place at the time of (first) BT will be performed
- GFR ≥ 50 mL/min
- Patient informed consent
Exclusion Criteria:
- Other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin
- Small cell neuroendocrine cancer, melanoma and other rare cancers in the cervix
- Metastatic disease beyond intervertebral disc L2/3 level
- Previous pelvic or abdominal radiotherapy
- Previous total or subtotal hysterectomy
- Combination of preoperative radiotherapy with surgery
- Patients receiving BT only
- Patients receiving EBRT only
- Patients receiving neo-adjuvant chemotherapy or other forms of antineoplastic treatment apart from weekly concomitant cisplatin (40 mg/m2).
- Contra-indications to MRI
- Contra-indications to BT
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: HYPO + iREX
Participants receive hypofractionated whole pelvic radiotherapy with concurrent chemotherapy followed by image-guided adaptive brachytherapy optimized using iRex in addition to standard D2cc constraints.
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Whole pelvic radiotherapy delivered using hypofractionation (2.2 Gy per fraction over 20 fractions) with IMRT.
Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
Image-guided adaptive brachytherapy delivered following external beam radiotherapy.
Brachytherapy treatment planning optimized using iReX in addition to standard D2cc constraints.
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Experimental: HYPO + Standard Planning
Participants receive hypofractionated whole pelvic radiotherapy with concurrent chemotherapy followed by image-guided adaptive brachytherapy using standard D2cc constraints without iRex optimization.
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Whole pelvic radiotherapy delivered using hypofractionation (2.2 Gy per fraction over 20 fractions) with IMRT.
Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
Image-guided adaptive brachytherapy delivered following external beam radiotherapy.
Conventional brachytherapy treatment planning using standard D2cc constraints without iReX optimization.
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Comparador Ativo: CVRT + iREX
Participants receive conventional fractionated whole pelvic radiotherapy with concurrent chemotherapy followed by image-guided adaptive brachytherapy optimized using iRex.
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Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
Image-guided adaptive brachytherapy delivered following external beam radiotherapy.
Brachytherapy treatment planning optimized using iReX in addition to standard D2cc constraints.
Whole pelvic radiotherapy delivered using conventional fractionation (1.8 Gy per fraction over 25 fractions) with IMRT.
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Comparador Ativo: CVRT + Standard Planning
Participants receive conventional fractionated whole pelvic radiotherapy with concurrent chemotherapy followed by image-guided adaptive brachytherapy using standard planning without iRex.
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Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
Image-guided adaptive brachytherapy delivered following external beam radiotherapy.
Conventional brachytherapy treatment planning using standard D2cc constraints without iReX optimization.
Whole pelvic radiotherapy delivered using conventional fractionation (1.8 Gy per fraction over 25 fractions) with IMRT.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Incidence of Acute Treatment-Related Toxicity
Prazo: During treatment and up to 3 months after completion of radiotherapy
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Incidence of acute treatment-related toxicity during radiotherapy and at 1- and 3-month follow-up after treatment, assessed using CTCAE version 5.0.
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During treatment and up to 3 months after completion of radiotherapy
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Incidence of Late (Chronic) Treatment-Related Toxicity
Prazo: From 6 months up to 5 years after completion of radiotherapy
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Incidence of late (chronic) treatment-related toxicity assessed at 6 and 12 months, and at 3 and 5 years after treatment using CTCAE version 5.0.
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From 6 months up to 5 years after completion of radiotherapy
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Tumor Response Rate
Prazo: Up to 12 months after completion of radiotherapy
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Tumor response rate assessed after external beam radiotherapy and at 3-, 6-, and 12-month follow-up.
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Up to 12 months after completion of radiotherapy
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Quality of Life Assessed by EQ-5D-5L
Prazo: During treatment and up to 5 years after completion of radiotherapy
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Patient-reported quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) during treatment and at 1-, 3-, 6-, and 12-month, and 3- and 5-year follow-up. The EQ-5D-5L descriptive system assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression across 5 levels of severity. The EQ Visual Analog Scale (EQ-VAS) ranges from 0 to 100, with higher scores indicating better perceived health status. |
During treatment and up to 5 years after completion of radiotherapy
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Local Recurrence-free Survival
Prazo: At 3 and 5 years after completion of radiotherapy
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Time from completion of radiotherapy to local tumor recurrence.
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At 3 and 5 years after completion of radiotherapy
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Nodal Recurrence-free Survival
Prazo: At 3 and 5 years after completion of radiotherapy.
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Time from completion of radiotherapy to nodal recurrence.
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At 3 and 5 years after completion of radiotherapy.
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Distant Metastasis-free Survival
Prazo: At 3 and 5 years after completion of radiotherapy.
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Time from completion of radiotherapy to distant metastasis.
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At 3 and 5 years after completion of radiotherapy.
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Disease-specific Survival
Prazo: At 3 and 5 years after completion of radiotherapy.
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Time from completion of radiotherapy to death due to cervical cancer.
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At 3 and 5 years after completion of radiotherapy.
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Overall Survival
Prazo: At 3 and 5 years after completion of radiotherapy.
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Time from completion of radiotherapy to death from any cause.
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At 3 and 5 years after completion of radiotherapy.
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Correlation of Dosimetric Parameters With Tumor Control and Toxicity
Prazo: During treatment and follow-up up to 5 years after completion of radiotherapy.
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Exploratory analyses will assess the correlation between dosimetric parameters from brachytherapy treatment planning, including dose-volume histogram (DVH) metrics and iRex optimization values, and clinical outcomes, including local tumor control and incidence of treatment-related gastrointestinal and genitourinary toxicities assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
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During treatment and follow-up up to 5 years after completion of radiotherapy.
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High-risk Clinical Target Volume D90 Comparison Between iRex-oriented and Conventional Brachytherapy Planning
Prazo: From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
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Comparison of high-risk clinical target volume (HR-CTV) D90 dose between iRex-oriented optimization and conventional brachytherapy planning.
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From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
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Number of Brachytherapy Fractions Achieving Successful iRex Optimization
Prazo: From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
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Number and percentage of brachytherapy fractions achieving successful iRex-oriented dose optimization according to predefined planning objectives.
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From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
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Dose-Response Relationship Between iRex and Toxicity
Prazo: During follow-up up to 5 years
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Evaluation of the relationship between iRex values and treatment-related toxicity.
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During follow-up up to 5 years
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Incremental Cost-effectiveness Ratio per Quality-adjusted Life Year Between Hypofractionated and Conventional Radiotherapy
Prazo: During treatment and follow-up up to 5 years after completion of radiotherapy.
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Cost and utility data will be used to evaluate cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER) between hypofractionated and conventional radiotherapy.
Uncertainty analyses will be performed using oneway sensitivity analysis, probabilistic sensitivity analysis, and threshold analysis.
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During treatment and follow-up up to 5 years after completion of radiotherapy.
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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)
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Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
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Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Doenças Genitais
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Doenças uterinas
- Doenças Genitais Femininas
- Neoplasias Genitais Femininas
- Doenças do colo do útero
- Neoplasias uterinas
- Neoplasias do colo uterino
- Terapêutica
- Radioterapia
- Fracionamento da dose, radiação
- Dosagem de radioterapia
- Hipofracionamento da dose de radiação
Outros números de identificação do estudo
- Si 149/2564(IRB3)
Plano para dados de participantes individuais (IPD)
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