Online Adaptive Radiotherapy With a Boost to the Primary Tumor and Clinically Involved Lymph Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: A Prospective, Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- pCR
研究概览
简要总结
This prospective, single-center, randomized controlled trial evaluates whether online adaptive radiotherapy (ART) with a sequential boost to both the primary rectal tumor and clinically involved lymph nodes improves pathologic complete response in patients with high-risk, node-positive locally advanced rectal cancer. Participants were randomly assigned 1:1 to online ART with a sequential boost or conventional non-adaptive intensity-modulated radiotherapy (IMRT). Both groups received concurrent capecitabine during long-course chemoradiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision. The planned sample size was 128 participants. Enrollment was discontinued after an interim review after 76 participants had been randomized; long-term follow-up of enrolled participants is ongoing.
详细描述
The trial was originally designed to evaluate adaptive dose escalation to the primary rectal tumor and clinically involved lymph nodes during neoadjuvant treatment for locally advanced rectal cancer. During trial conduct, the protocol was amended to reflect the treatment strategy implemented in the enrolled cohort. Enrollment was operationally consolidated at the lead center. Online ART was delivered using either MR-guided or CBCT-guided workflows. In the experimental arm, a sequential boost of 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary tumor and clinically involved lymph nodes, followed by online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. The control arm received conventional non-adaptive IMRT to 50 Gy in 25 fractions without dose escalation. Both groups received concurrent capecitabine and 3-4 cycles of CAPEOX consolidation chemotherapy.
The planned enrollment was 128 participants. During trial conduct, an interim review was undertaken after 76 participants had been randomized. The interim analysis had not been specified in the original protocol and no formal group-sequential efficacy or futility boundary had been prespecified. Enrollment was subsequently discontinued, while protocol-defined follow-up of enrolled participants continues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older.
- •ECOG performance status of 0 or
- •Histologically confirmed rectal adenocarcinoma.
- •Primary tumor located within 10 cm of the anal verge by pelvic MRI and/or rigid sigmoidoscopy.
- •Clinically involved regional lymph nodes (cN1-2) according to the AJCC 8th edition.
- •At least one additional high-risk feature: cT4 disease, cN2 disease, extramural vascular invasion, mesorectal fascia involvement, lateral pelvic lymph-node involvement, tumor deposits, or low rectal cancer (≤5 cm from the anal verge).
- •Baseline locoregional staging with contrast-enhanced pelvic MRI and chest/abdominal imaging excluding distant metastases.
- •Treatment-naïve with respect to systemic therapy and pelvic radiotherapy for the index rectal cancer and suitable for total mesorectal excision.
- •Adequate organ function and no medical contraindication to chemoradiotherapy.
- •Written informed consent before study-specific procedures.
排除标准
- •Prior pelvic radiotherapy.
- •Prior rectal surgery for the index cancer, including local excision or transanal procedures.
- •Radiologically or pathologically confirmed distant metastasis.
- •Locally recurrent rectal cancer.
- •Active inflammatory bowel disease.
- •History of another primary malignancy within the preceding 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ.
- •Pregnancy or lactation.
- •Severe or uncontrolled medical condition contraindicating chemoradiotherapy or surgery.
- •Clinically significant hypersensitivity to protocol systemic therapy that precludes treatment.
研究组 & 干预措施
Online ART With Sequential Boost
Participants received online adaptive radiotherapy using MR- or CBCT-guided workflows. A sequential boost of either 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary rectal tumor (GTVp) and clinically involved lymph nodes (GTVn), followed by continued online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: Online Adaptive Radiotherapy With Sequential Boost (Radiation)
Online ART With Sequential Boost
Participants received online adaptive radiotherapy using MR- or CBCT-guided workflows. A sequential boost of either 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary rectal tumor (GTVp) and clinically involved lymph nodes (GTVn), followed by continued online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: CAPEOX (Drug)
Online ART With Sequential Boost
Participants received online adaptive radiotherapy using MR- or CBCT-guided workflows. A sequential boost of either 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary rectal tumor (GTVp) and clinically involved lymph nodes (GTVn), followed by continued online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: Total Mesorectal Excision (Procedure)
Online ART With Sequential Boost
Participants received online adaptive radiotherapy using MR- or CBCT-guided workflows. A sequential boost of either 9 Gy in 3 fractions or 10 Gy in 2 fractions was delivered to the primary rectal tumor (GTVp) and clinically involved lymph nodes (GTVn), followed by continued online ART to 50 Gy in 25 fractions to the pelvic clinical target volume. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: Capecitabine (Drug)
Conventional Non-Adaptive IMRT
Participants received conventional non-adaptive intensity-modulated radiotherapy to the pelvic clinical target volume at 50 Gy in 25 fractions without dose escalation. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: Conventional Non-Adaptive IMRT (Radiation)
Conventional Non-Adaptive IMRT
Participants received conventional non-adaptive intensity-modulated radiotherapy to the pelvic clinical target volume at 50 Gy in 25 fractions without dose escalation. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: CAPEOX (Drug)
Conventional Non-Adaptive IMRT
Participants received conventional non-adaptive intensity-modulated radiotherapy to the pelvic clinical target volume at 50 Gy in 25 fractions without dose escalation. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: Total Mesorectal Excision (Procedure)
Conventional Non-Adaptive IMRT
Participants received conventional non-adaptive intensity-modulated radiotherapy to the pelvic clinical target volume at 50 Gy in 25 fractions without dose escalation. Concurrent capecitabine was administered during radiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision.
干预措施: Capecitabine (Drug)
结局指标
主要结局
pCR
时间窗: 1 year
primary tumor achieved pathological complete response
surgical difficulty
时间窗: 2 years
The difficulty score of a surgery is calculated through a comprehensive assessment of the following indicators: surgical blood loss, surgical blood loss, pelvic fibrosis, pelvic fibrosis, degree of edema, number of anastomotic fistulas, and number of urinary dysfunctions.
pCR
时间窗: At total mesorectal excision after completion of neoadjuvant therapy, up to approximately 6 months after randomization
Proportion of participants achieving ypT0N0, defined as absence of viable tumor cells in the resected primary tumor and regional lymph nodes after neoadjuvant treatment.
次要结局
- cCR(2 years)
- 3-year overal survival rate(3 years)
- 5-year overal survival rate(5 years)
- 3-year disease free suvival rate(3 years)
- 5-year disease free suvival rate(5 years)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(3 years)
- The Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system(3 years)
- Quality of life assessment using the EORTC QLQ-C30 questionnaire(3 year)
- Quality of life assessment using the EORTC QLQ-CR29 questionnaire(3 years)
- Surgical Difficulty(Time Frame: Perioperative through 30 days after surgery)
- Clinical Complete Response (cCR) Rate(At preoperative restaging after completion of neoadjuvant therapy, before planned surgery)
- 3-year disease free survival rate(3 years)
- Treatment-related adverse events(1 year)
- Perioperative complications(From surgery through 30 days after surgery)
- Perineal wound healing after APR(Through 6 months after surgery)
研究者
Jinbo Yue
Shandong Cancer Hospital and Institute
Shandong Cancer Hospital and Institute