A Prospective Single-Arm Phase II Study of Pelvic External Beam Radiotherapy Followed by HDR Endorectal Brachytherapy Combined With a 3D-Printed Individualized Guide Template and Tungsten-Alloy Local Shielding for Organ Preservation in Inoperable Localized Rectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- 12-Month Clinical Complete Response Rate
研究概览
简要总结
This prospective, single-center, single-arm phase II study will evaluate the efficacy, safety, and technical feasibility of an organ-preserving radiotherapy strategy for patients with localized rectal adenocarcinoma who are medically inoperable, decline radical surgery, or are considered technically unresectable without distant metastases.
Participants will receive pelvic external beam radiotherapy followed by high-dose-rate (HDR) endorectal brachytherapy. Concurrent capecitabine may be given during external beam radiotherapy to participants who are considered able to tolerate chemotherapy. During HDR brachytherapy, all participants will be treated using a patient-specific 3D-printed guide template and individualized tungsten-alloy local shielding. The guide template is designed to improve applicator positioning and treatment reproducibility, while the local shielding is intended to reduce radiation exposure to non-target rectal wall.
The study will enroll 50 participants. The primary objectives are to evaluate the 12-month clinical complete response rate and the technical completion rate of the HDR brachytherapy platform. Secondary assessments include organ preservation, local regrowth, survival outcomes, treatment-related toxicity, quality of life, and anorectal function.
详细描述
This investigator-initiated study is a prospective, open-label, single-arm phase II trial evaluating a definitive non-operative treatment strategy for localized rectal cancer. Eligible participants will have histologically confirmed rectal adenocarcinoma without distant metastases and will be considered medically unsuitable for radical surgery, decline radical surgery after appropriate counseling, or be considered technically unresectable by multidisciplinary assessment.
Following baseline evaluation and multidisciplinary review, participants will receive pelvic external beam radiotherapy. The planned dose to the pelvic planning target volume is 45 Gy in 25 fractions. Radiologically positive or highly suspicious lymph nodes will receive a simultaneous integrated boost to 55 Gy in 25 fractions, with escalation to 58-58.25 Gy in 25 fractions permitted when considered dosimetrically safe. Concurrent capecitabine at 825 mg/m² twice daily on radiotherapy days may be administered to participants who are considered able to tolerate chemotherapy; concurrent chemotherapy is not mandatory in this study.
Participants will undergo reassessment approximately 4-6 weeks after completion of external beam radiotherapy before proceeding to HDR endorectal brachytherapy. The planned HDR boost is 6 Gy per fraction for 3 fractions using an iridium-192 source, with fractions generally separated by 5-7 days.
During all HDR fractions, a patient-specific 3D-printed guide template will be used for applicator positioning, fixation, and reproducibility. Individualized flexible tungsten-alloy shielding, typically approximately 3 mm thick, will be positioned within a predefined channel in the template before treatment. The shielding configuration will be individualized according to tumor distribution and the location of non-target rectal wall requiring protection. Because the shielding material may produce substantial computed tomography artifacts, treatment planning will be performed before placement of the tungsten-alloy shielding, followed by verification of shielding direction, depth, and fixation before irradiation.
Tumor response will be assessed using a combination of digital rectal examination, endoscopy, and pelvic magnetic resonance imaging. Participants achieving a clinical complete response will enter a structured watch-and-wait follow-up program. Participants with residual disease, local regrowth, or progression will undergo multidisciplinary reassessment for individualized salvage treatment when appropriate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years.
- •Histologically confirmed rectal adenocarcinoma.
- •Clinical stage cT2-4, any N, M
- •Patients who are elderly or frail, medically unsuitable for radical surgery, refuse radical surgery, or are considered by a multidisciplinary team (MDT) to have disease for which safe R0 resection is technically difficult.
- •Considered by the MDT and investigators to be suitable for a definitive non-operative treatment strategy.
- •ECOG performance status 0-2; patients with ECOG performance status 3 may be eligible if considered by the MDT to be able to tolerate the study treatment.
- •Estimated life expectancy of at least 6 months.
- •Considered suitable for pelvic external beam radiotherapy and HDR endorectal brachytherapy.
- •Tumor location, endorectal access, and local anatomy suitable for HDR brachytherapy using the individualized 3D-printed guide template.
- •Adequate hematologic, hepatic, and renal function for the planned treatment.
- •Ability to understand the study requirements and provide written informed consent.
排除标准
- •Distant metastatic disease or disease considered unsuitable for definitive local non-operative treatment.
- •Prior definitive pelvic radiotherapy.
- •Intestinal perforation, complete bowel obstruction, uncontrolled active bleeding, or severe active infection.
- •Anatomical or clinical conditions precluding HDR endorectal brachytherapy or use of the individualized guide template/local shielding platform.
- •Inflammatory bowel disease.
- •Severe uncontrolled cardiopulmonary disease, significant bone marrow suppression, or severe hepatic or renal dysfunction.
- •Pregnancy or breastfeeding.
- •Concurrent participation in another clinical trial that may interfere with evaluation of the study treatment or endpoints.
- •Any other condition considered by the investigator to make the patient unsuitable for participation in the study.
研究组 & 干预措施
HDR Brachytherapy-Based Organ Preservation
Participants will receive definitive organ-preserving treatment for rectal cancer, including external beam radiotherapy with concurrent chemotherapy as clinically indicated, followed by high-dose-rate brachytherapy for local dose intensification. Patient-specific treatment planning and study-specific brachytherapy techniques will be performed according to the study protocol.
干预措施: High-Dose-Rate Endorectal Brachytherapy (Radiation)
结局指标
主要结局
12-Month Clinical Complete Response Rate
时间窗: From completion of study treatment through 12 months
Percentage of participants who maintain a clinical complete response (cCR) at 12 months after completion of study treatment, without local regrowth and without rectal cancer-related salvage resection. Clinical response will be assessed using a composite evaluation including digital rectal examination, endoscopy, and pelvic magnetic resonance imaging.
Technical Completion Rate of HDR Brachytherapy
时间窗: Through completion of HDR brachytherapy, approximately 8-10 weeks after completion of external beam radiotherapy
Percentage of participants who complete all three planned high-dose-rate (HDR) endorectal brachytherapy fractions using the study-specific 3D-printed individualized guide template and tungsten alloy local shielding platform as required by the study protocol.
次要结局
- Overall Clinical Complete Response Rate(From completion of study treatment through 12 months)
- Near-Clinical Complete Response Rate(From completion of study treatment through 12 months)
- 12-Month Organ Preservation Rate(From completion of study treatment through 12 months)
- Local Regrowth Rate(From completion of study treatment through 24 months)
- Local Failure-Free Survival(from enrollment through 24 months)
- Progression-Free Survival(from enrollment through 24 months)
- Overall Survival(from enrollment through 24 months)
- Stoma-Free Survival(from enrollment through 24 months)
- Incidence of Acute Treatment-Related Adverse Events(From initiation of study treatment through 90 days after completion of study treatment)
- Incidence of Late Treatment-Related Adverse Events(From more than 90 days after completion of study treatment through 24 months)