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.
研究概览
地位
条件
详细说明
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.
研究类型
注册 (实际的)
阶段
- 不适用
联系人和位置
学习地点
-
-
Bangkok
-
Bangkok、Bangkok、泰国
- Siriraj Hospital
-
-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：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.
|
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.
|
|
实验性的：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.
|
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.
|
|
有源比较器：CVRT + iREX
Participants receive conventional fractionated whole pelvic radiotherapy with concurrent chemotherapy followed by image-guided adaptive brachytherapy optimized using iRex.
|
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.
|
|
有源比较器：CVRT + Standard Planning
Participants receive conventional fractionated whole pelvic radiotherapy with concurrent chemotherapy followed by image-guided adaptive brachytherapy using standard planning without iRex.
|
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.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Incidence of Acute Treatment-Related Toxicity
大体时间：During treatment and up to 3 months after completion of radiotherapy
|
Incidence of acute treatment-related toxicity during radiotherapy and at 1- and 3-month follow-up after treatment, assessed using CTCAE version 5.0.
|
During treatment and up to 3 months after completion of radiotherapy
|
|
Incidence of Late (Chronic) Treatment-Related Toxicity
大体时间：From 6 months up to 5 years after completion of radiotherapy
|
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.
|
From 6 months up to 5 years after completion of radiotherapy
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Tumor Response Rate
大体时间：Up to 12 months after completion of radiotherapy
|
Tumor response rate assessed after external beam radiotherapy and at 3-, 6-, and 12-month follow-up.
|
Up to 12 months after completion of radiotherapy
|
|
Quality of Life Assessed by EQ-5D-5L
大体时间：During treatment and up to 5 years after completion of radiotherapy
|
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
|
|
Local Recurrence-free Survival
大体时间：At 3 and 5 years after completion of radiotherapy
|
Time from completion of radiotherapy to local tumor recurrence.
|
At 3 and 5 years after completion of radiotherapy
|
|
Nodal Recurrence-free Survival
大体时间：At 3 and 5 years after completion of radiotherapy.
|
Time from completion of radiotherapy to nodal recurrence.
|
At 3 and 5 years after completion of radiotherapy.
|
|
Distant Metastasis-free Survival
大体时间：At 3 and 5 years after completion of radiotherapy.
|
Time from completion of radiotherapy to distant metastasis.
|
At 3 and 5 years after completion of radiotherapy.
|
|
Disease-specific Survival
大体时间：At 3 and 5 years after completion of radiotherapy.
|
Time from completion of radiotherapy to death due to cervical cancer.
|
At 3 and 5 years after completion of radiotherapy.
|
|
Overall Survival
大体时间：At 3 and 5 years after completion of radiotherapy.
|
Time from completion of radiotherapy to death from any cause.
|
At 3 and 5 years after completion of radiotherapy.
|
|
Correlation of Dosimetric Parameters With Tumor Control and Toxicity
大体时间：During treatment and follow-up up to 5 years after completion of radiotherapy.
|
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.
|
During treatment and follow-up up to 5 years after completion of radiotherapy.
|
|
High-risk Clinical Target Volume D90 Comparison Between iRex-oriented and Conventional Brachytherapy Planning
大体时间：From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
|
Comparison of high-risk clinical target volume (HR-CTV) D90 dose between iRex-oriented optimization and conventional brachytherapy planning.
|
From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
|
|
Number of Brachytherapy Fractions Achieving Successful iRex Optimization
大体时间：From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
|
Number and percentage of brachytherapy fractions achieving successful iRex-oriented dose optimization according to predefined planning objectives.
|
From treatment initiation through completion of brachytherapy treatment, an average of 4 weeks.
|
|
Dose-Response Relationship Between iRex and Toxicity
大体时间：During follow-up up to 5 years
|
Evaluation of the relationship between iRex values and treatment-related toxicity.
|
During follow-up up to 5 years
|
|
Incremental Cost-effectiveness Ratio per Quality-adjusted Life Year Between Hypofractionated and Conventional Radiotherapy
大体时间：During treatment and follow-up up to 5 years after completion of radiotherapy.
|
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.
|
During treatment and follow-up up to 5 years after completion of radiotherapy.
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- Si 149/2564(IRB3)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.