Simultaneous Boost in Neoadjuvant Radiotherapy for Rectal Cancer：A Phase 2, Randomized Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- CR
研究概览
简要总结
The goal of this clinical trial is to learn whether new adjuvant radiotherapy with gross tumor volume(GTV) escalated to 58.75 Gy can improve complete response (CR) rates compared with GTV dose of 50 Gy in adult patients (18-79 years) with locally advanced rectal adenocarcinoma (T3-T4/N+, M0) located ≤10 cm from the anal verge.The main questions it aims to answer are:
- Does GTV simultaneously boost to 58.75 Gy/25f increase complete response (pCR or cCR) compared with 50 Gy/25f?
- How do the two regimens differ in terms of progression-free survival (PFS), pelvic local control (LC), tumor regression grade (TRG), organ preservation, and treatment-related toxicity? Researchers will compare GTV 58.75 Gy/25f (experimental arm) versus GTV 50 Gy/25f (control arm) to see if dose escalation improves tumor response rate.
Participants will:
- Receive neoadjuvant radiotherapy with one of the two PGTV dose escalated regimens (with concurrent chemotherapy: oral capecitabine or XELOX).
- Undergo restaging with imaging and clinical assessment before surgery or observation.
- Proceed to total mesorectal excision (TME), local excision, or "watch-and-wait" strategy depending on treatment response and patient preference.
- Be followed regularly with clinical exams, imaging, endoscopy, and laboratory tests to assess efficacy, safety, and long-term outcomes.
详细描述
This study is a randomized controlled trial designed to evaluate the clinical efficacy and safety of simultaneous integrated boost (SIB) dose escalation in the neoadjuvant treatment of locally advanced rectal cancer (LARC).Standard neoadjuvant chemoradiotherapy (nCRT) typically utilizes a dose of 50 Gy to the gross tumor volume (GTV). This trial investigates whether escalating the radiation dose specifically to the GTV to 58.75 Gy, delivered in 25 fractions, can significantly enhance tumor downstaging and increase the rates of pathologic complete response (pCR) or sustained clinical complete response (cCR).Study Arms and Radiation Technique:Participants are randomized into two arms. Both arms receive intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) with concurrent fluoropyrimidine-based chemotherapy.Experimental Arm: The planned target volume of the GTV (PGTV) receives a total dose of 58.75 Gy in 25 fractions ($2.35 \text{ Gy/fraction}$), while the elective lymphatic drainage areas (PTV) receive 45-50 Gy.Control Arm: The PGTV receives a total dose of 50 Gy in 25 fractions ($2.0 \text{ Gy/fraction}$), consistent with standard-of-care protocols.Clinical Workflow:Following the completion of neoadjuvant therapy, patients will undergo a mandatory restaging assessment 6-12 weeks post-radiation. This evaluation includes digital rectal examination (DRE), pelvic multiparametric MRI (mpMRI), and endoscopy.Surgical Intervention and Organ Preservation:Patients achieving a cCR may be offered a "Watch-and-Wait" (W&W) strategy with intensive surveillance, aiming for organ preservation.Patients with a good but incomplete response may undergo local excision (LE) or total mesorectal excision (TME).The primary endpoint is the combined complete response (CR) rate, defined as pCR for those undergoing surgery and cCR (sustained for at least 6 months) for those entering the W&W protocol.Secondary Objectives:The study will also perform a comparative analysis of progression-free survival (PFS), local control (LC) rates, and the distribution of Tumor Regression Grade (TRG). Safety profiles will be rigorously monitored using the Common Terminology Criteria for Adverse Events (CTCAE), focusing on acute and late gastrointestinal and genitourinary toxicities.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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 and <80 years
- •Histologically confirmed rectal adenocarcinoma
- •Tumor located within 10 cm from the anal verge
- •MRI staging: T3-T4 and/or N+, M0 (AJCC 8th edition)
- •ECOG performance status 0-2
- •Adequate bone marrow function: WBC ≥3×10⁹/L, ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L
- •Adequate liver function: TBIL ≤1.5 × ULN, ALT/AST ≤2.5 × ULN
- •Adequate renal function: Cr ≤1.5 × ULN or CCr ≥60 mL/min
- •Signed informed consent
排除标准
- •Prior rectal cancer surgery
- •Prior induction chemotherapy, immunotherapy, or pelvic radiotherapy
- •History of other malignancies
- •History of chronic colitis, ulcerative colitis, or nonspecific proctitis
- •Pregnant or breastfeeding women
- •Active infection or fever
- •Severe uncontrolled comorbidities (e.g., unstable heart disease, renal disease, chronic hepatitis, uncontrolled diabetes, psychiatric disorders)
- •Inability to comply with study protocol
研究组 & 干预措施
Experimental Arm (GTV 58.75 Gy/25f)
Radiotherapy: long course simultaneous integrated boost radiotherapy
- Gross tumor volume (GTV): A total dose of 58.75Gy delivered in 25 fractions using a simultaneous integrated boost approach.
- CTV: 45Gy/25f
- Mesorectum lymph node(GTVnd1):58.75Gy/25f
- Lateral lymph node（GTVnd2）：60Gy/25f Concurrent Chemotherapy: Concurrent administration of capecitabine (825 mg/m² twice daily, 5 days per week) or XELOX regimen during radiotherapy After treatment, patients will undergo restaging and proceed to total mesorectal excision (TME) or non-operative management ("watch-and-wait") depending on response and clinical assessment.
干预措施: GTV 58.75 Gy/25 fractions(Simultaneous Integrated Boost) (Radiation)
Experimental Arm (GTV 58.75 Gy/25f)
Radiotherapy: long course simultaneous integrated boost radiotherapy
- Gross tumor volume (GTV): A total dose of 58.75Gy delivered in 25 fractions using a simultaneous integrated boost approach.
- CTV: 45Gy/25f
- Mesorectum lymph node(GTVnd1):58.75Gy/25f
- Lateral lymph node（GTVnd2）：60Gy/25f Concurrent Chemotherapy: Concurrent administration of capecitabine (825 mg/m² twice daily, 5 days per week) or XELOX regimen during radiotherapy After treatment, patients will undergo restaging and proceed to total mesorectal excision (TME) or non-operative management ("watch-and-wait") depending on response and clinical assessment.
干预措施: Concurrent Chemotherapy (Drug)
Experimental Arm (GTV 58.75 Gy/25f)
Radiotherapy: long course simultaneous integrated boost radiotherapy
- Gross tumor volume (GTV): A total dose of 58.75Gy delivered in 25 fractions using a simultaneous integrated boost approach.
- CTV: 45Gy/25f
- Mesorectum lymph node(GTVnd1):58.75Gy/25f
- Lateral lymph node（GTVnd2）：60Gy/25f Concurrent Chemotherapy: Concurrent administration of capecitabine (825 mg/m² twice daily, 5 days per week) or XELOX regimen during radiotherapy After treatment, patients will undergo restaging and proceed to total mesorectal excision (TME) or non-operative management ("watch-and-wait") depending on response and clinical assessment.
干预措施: Total mesorectal excision (TME) surgery or non-operative management (Procedure)
Control Arm (PGTV 50 Gy/25f)
Radiotherapy: long course simultaneous integrated boost radiotherapy Gross tumor volume (GTV): A total dose of 50Gy delivered in 25 fractions using a simultaneous integrated boost approach.
CTV: 45Gy/25f Mesorectum lymph node(GTVnd1):58.75Gy/25f Lateral lymph node（GTVnd2）：60Gy/25f Concurrent Chemotherapy: Concurrent administration of capecitabine (825 mg/m² twice daily, 5 days per week) or XELOX regimen during radiotherapy After treatment, patients will undergo restaging and proceed to total mesorectal excision (TME) or non-operative management ("watch-and-wait") depending on response and clinical assessment.
干预措施: GTV 50 Gy/25 fractions(Simultaneous Integrated Boost) (Radiation)
Control Arm (PGTV 50 Gy/25f)
Radiotherapy: long course simultaneous integrated boost radiotherapy Gross tumor volume (GTV): A total dose of 50Gy delivered in 25 fractions using a simultaneous integrated boost approach.
CTV: 45Gy/25f Mesorectum lymph node(GTVnd1):58.75Gy/25f Lateral lymph node（GTVnd2）：60Gy/25f Concurrent Chemotherapy: Concurrent administration of capecitabine (825 mg/m² twice daily, 5 days per week) or XELOX regimen during radiotherapy After treatment, patients will undergo restaging and proceed to total mesorectal excision (TME) or non-operative management ("watch-and-wait") depending on response and clinical assessment.
干预措施: Concurrent Chemotherapy (Drug)
Control Arm (PGTV 50 Gy/25f)
Radiotherapy: long course simultaneous integrated boost radiotherapy Gross tumor volume (GTV): A total dose of 50Gy delivered in 25 fractions using a simultaneous integrated boost approach.
CTV: 45Gy/25f Mesorectum lymph node(GTVnd1):58.75Gy/25f Lateral lymph node（GTVnd2）：60Gy/25f Concurrent Chemotherapy: Concurrent administration of capecitabine (825 mg/m² twice daily, 5 days per week) or XELOX regimen during radiotherapy After treatment, patients will undergo restaging and proceed to total mesorectal excision (TME) or non-operative management ("watch-and-wait") depending on response and clinical assessment.
干预措施: Total mesorectal excision (TME) surgery or non-operative management (Procedure)
结局指标
主要结局
CR
时间窗: 1 year
primary tumor achieved pathological complete response or clinical complete response.
次要结局
- 3-year disease free suvival rate(3 years)
- 3-year local control rate(3 years)
- Tumor Regression Grade(1 year)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(3 years)
- Organ Preservation Rate(1 year)