Sentinel Lymph Node Sampling for Patients With Middle-high Risk Endometrial Cancer Confined to the Uterus

Prognosis Clinical Trial

Official title:

Sentinel Lymph Node Sampling Versus Systematic Pelvic Lymphadenectomy on the Prognosis for Patients With Middle-high Risk Endometrial Cancer Confined to the Uterus Before Surgery: a Non-inferiority Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04276532
• Other study ID #: V01 2019-12
• Status: Recruiting
• Phase: N/A
• Start date: February 13, 2020
• Est. completion date: February 12, 2028

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: Xiaojun Chen, Ph.D
• Phone: 862163455050
• Email: cxjlhjj[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim To investigate the effect of sentinel lymph node (SLN) sampling on the prognosis of patients with middle-high risk endometrial cancer obviously confined to the uterus before surgery.

Description:

Aim to investigate the effect of sentinel lymph node (SLN) sampling on the prognosis of patients with middle-high risk endometrial cancer obviously confined to the uterus before surgery.

Rationale The diagnostic value of sentinel lymph node sampling has been widely approved. NCCN guideline suggested that "SLN mapping can be considered for the surgical staging of apparent uterine-confined malignancy when there is no metastasis demonstrated by imaging studies or no obvious extrauterine disease at exploration". However, the role of SLN in the prognosis of mid-high risk endometrial cancer clinically confined to the uterus is unclear. There are big concerns that SLN sampling only without lymph node dissection might miss isolated para-aortic lymph node metastasis or remain lymph node with metastasis other than SLN unremoved and thus affect the prognosis of patients. NCCN also suggested that "Para-aortic nodal evaluation from the inframesenteric and infraenal regions may also be utilized for staging in women with high-risk tumors such as deeply invasive lesions, high-grade histology, and tumors of serous carcinoma, clear cell carcinoma or carcinosarcoma. Thus, it is necessary to carry out a randomized trail to investigate the role of SLN in the prognosis of middle-high risk endometrial cancer obviously confined to the uterus before surgery.

Ethnics This study were approved by the Ethics Committees of Obstetrics and Gynecology Hospital of Fudan University and all other institutes. Before initiation of study procedures, written informed consent will be obtained from each patient regarding risks of treatments and agreement of using their clinical data for research purpose.

Randomization and Treatment This is a multicentered, open-label, randomized clinical trial. Randomization will be carried out in each center. A computer-based procedure of simple randomization (SPSS for Mac, version 22.0; IBM ) will be used for participant enrollment and randomization. Before an individual is successfully enrolled, her treatment assignment will remain concealed. This trial will be open label: patients and study physicians were aware of treatment assignment.

Eligible patients in each center will be randomly assigned (1:1) to receive:

1. Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus pelvic lymphonodectomy (PLN) with para-aortic sampling, or 2. Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus sentinel lymph node sampling (SLN).

1. The principles of surgery procedures and post-operative adjuvant therapies will follow the latest NCCN guidelines.

2. Surgery carried out by laparotomy, laparoscope, or robotic surgery are accepted.

3. Colored dyes including indocyanine green (ICG) (preferred), methylene blue, carbon nanotube for sentinel lymph node are accepted.

4. Postoperative adjuvant treatments are carried out following the latest NCCN guidelines according to doctors' choice.

Statistical analyses On the basis of data from previous studies (GOG249, FRACOGYN), the 2-year PFS is expected to be 88% in the PLN group and 87% in SLN group. SLN would be considered as inferior to PLN if the 2-year PFS in SLN group is higher than 80%. An accrual of 780 patients in 3 years will provide the study with adequate power (80%) to detect a clinically relevant absolute difference of 8% in 2-year PFS (88% vs 80%) between both groups (one-sided test, a=0.025), with a lost follow up rate ≤10% . Analyses will be done firstly by intention to treat.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 780
• Est. completion date: February 12, 2028
• Est. primary completion date: February 12, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Older than 18 years old;

2. Clinically diagnosed (by pre-surgical pathology and radiology) as primary endometrial cancer confined to uterus with middle-high risk factors:

1. Disease limited to the uterus on image study (MRI, CT or ultrasound);

2. including all histological types of endometrial cancer (endometrioid, serous, clear cell, carcinosarcoma, and undifferentiated carcinoma); not including uterine sarcoma

3. excluding low-risk endometrial cancer (endometrioid G 1-2 with pre-surgical endometrial lesion=2cm and myometrial invasion <50%);

4. with one or more middle-high risk factors including: endometrioid endometrial cancer G3, myometrial invasion =50%, tumor size=2cm, type II endometrial cancer; LVSI

5. diagnosis should be confirmed by at least two senior clinicians.

3. Be able to undergo staging surgery.

Exclusion Criteria:

1. During pregnancy or perinatal period;

2. With malignancies other than endometrial cancer;

3. With history of important organs transplantation;

4. With immune diseases requiring taking immunosuppressants

5. With severe mental illness or brain function disorders

6. With history of drug abuse;

7. Allergic to contrast agent;

8. Still participating in other clinical trials;

9. Not willing to accept surgery or trial protocol;

10. Not eligible for surgery;

11. Had hysterectomy, chemotherapy, radiotherapy, or hormone therapy before the trail;

12. Had retroperitoneum lymph node dissection for other reasons.

Related Conditions & MeSH terms

• Endometrial Neoplasms
• Middle-high Risk Endometrial Cancer
• Prognosis
• Sentinel Lymph Node Sampling

Intervention

Procedure:
• sentinel lymph node sampling (SLN)
Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus sentinel lymph node sampling (SLN). The principles of surgery procedures and post-operative adjuvant therapies will follow the latest NCCN guidelines; Surgery carried out by laparotomy, laparoscope, or robotic surgery are accepted; Colored dyes including indocyanine green (ICG) (preferred), methylene blue, carbon nanotube for sentinel lymph node are accepted.
• pelvic lymphonodectomy (PLN)
Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus pelvic lymphonodectomy (PLN) with para-aortic sampling

Locations

Country	Name	City	State
China	Obstetrics and Gynecology Hospital, Fudan University	Shanghai	Shanghai

Sponsors (6)

Lead Sponsor	Collaborator
Xiaojun Chen	Chongqing University Cancer Hospital, Fudan University, Sun Yat-sen University, Tongji Hospital, West China Second University Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The 2-year progression-free survival (2-year PFS)	The percentage of patients who have first relapse within 2 years after surgery (SLN or LND)	2 years
Secondary	The 5-year PFS	The percentage of patients who have first relapse within 5 years after surgery (SLN or LND)	5 years
Secondary	The 5-year overall survival (OS)	The percentage of patients who die within 5 years after surgery (SLN or LND)	5 years
Secondary	Adverse effect and quality of life (QOL)	The occurence rate of each adverse effects related to surgery (SLN or LND, the scores of each QOL survay	Adverse effect: during the surgery, 30 days after surgery; QQL: 1 month before surgery, 6 months, 12 months after surgery