A Prospective Multicentre Phase III Randomised Open Clinical Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 624
- 主要终点
- Loco-regional recurrence (LRR)
研究概览
简要总结
The purpose of this study is to compare the efficacy and toxicity of early stage endometrial cancer based on molecular classification and conventional risk stratification adjuvant therapy decision-making, and to provide high-quality evidence-based medical evidence for individualized adjuvant therapy selection under the guidance of fine stratification system of endometrial cancer.
详细描述
This is an investigator-initiated prospective, national multicentre, phase III, randomised, open, non-inferiority clinical study. The study hypothesis is that adjuvant radiotherapy decision for early-stage endometrial cancer which is based on molecular classification can achieve de-escalation of adjuvant treatment without reducing local tumour control and survival, thereby potentially further reducing radiotherapy-related toxicity and improving quality of life, compared to using conventional risk stratification. The primary endpoint of this study is the 3-year local recurrence rate.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-
- •Patients with newly histologically confirmed Endometrioid adenocarcinoma.
- •ECOG score 0-2
- •Surgery consisting of a total hysterectomy and bilateral salpingo-oophorectomy, pelvic lymphadenectomy or sentinel lymph node biopsy, with or without para-aortic lymphadenectomy, oophorectomy
- •Patients with FIGO staging(2009 edition) I or II and meet one of the following conditions:
- •Stage IA G1-2 with massive LVSI+ or age ≥ 60 years
- •Stage IA G3, regardless of LVSI status
- •Stage IB G1-3, regardless of LVSI status
- •Stage II, regardless of tumor grade and LVSI status
- •Patients can understand the study protocol and voluntarily participate in the study, and give written informed consent before treatment.
排除标准
- •Not FIGO stage I-II.
- •Residual tumor or positive margin.
- •Mixed carcinoma, sarcoma or carcinosarcoma
- •Previous history of malignant tumor
- •Previous history of pelvic radiotherapy
- •The interval between surgery and radiotherapy is more than 12 weeks.
- •With serious medical complications, such as heart disease, lung disease and other diseases that cannot tolerate the whole course of radiotherapy
研究组 & 干预措施
Molecular classification based treatment
Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group.
Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-.
Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-.
Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.
干预措施: Vaginal brachytherapy (Radiation)
Molecular classification based treatment
Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group.
Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-.
Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-.
Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.
干预措施: Pelvic external beam radiotherapy (Radiation)
Molecular classification based treatment
Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group.
Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-.
Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-.
Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.
干预措施: Observation (Other)
Molecular classification based treatment
Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group.
Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-.
Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-.
Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.
干预措施: Chemotherapy (Drug)
Conventional risk stratification based treatment
Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age>60, IA G3 or IB G1-2 regardless of LVSI status).
EBRT for high-intermediate risk (stage I B with G3, or stage II)
干预措施: Vaginal brachytherapy (Radiation)
Conventional risk stratification based treatment
Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age>60, IA G3 or IB G1-2 regardless of LVSI status).
EBRT for high-intermediate risk (stage I B with G3, or stage II)
干预措施: Pelvic external beam radiotherapy (Radiation)
Conventional risk stratification based treatment
Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age>60, IA G3 or IB G1-2 regardless of LVSI status).
EBRT for high-intermediate risk (stage I B with G3, or stage II)
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Loco-regional recurrence (LRR)
时间窗: 3-year
Loco-regional recurrence (LRR) is defined as the first recurrence in the vagina or pelvic cavity during follow-up, which was confirmed by imaging examination or biopsy pathology.
次要结局
- Failure free survival(FFS)(3-year,5-year)
- Overall survical(OS)(3-year,5-year)
- Cumulative vaginal recurrence(3-year,5-year)
- De-escalation rate of treatment(3-year)
- Incidence of Acute and lateToxicities(3-year,5-year)
- Cumulative pelvic recurrence(3-year,5-year)
- Distance metastasis(DM)(3-year,5-year)
- Health-related cancer-specific quality of life(3-year,5-year)
- Endometrial cancer related health care costs(3 years, 5 years)