Letrozole as Maintenance Therapy Versus Observation After Adjuvant Treatment on the Prognosis for Post-surgical Endometrial Cancer Patients With Non-specific Molecular Profile: a Superiority Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- the 3-year Progression-Free-Survival(PFS)
研究概览
简要总结
Aim to investigate the effect of Letrozole as maintenance after adjuvant treatment on the prognosis of post-operative endometrial cancer patients with non-specific molecular profile.
详细描述
This is an open label multi-center superiority randomized controlled trial, aimed to investigate the effect of Letrozole as maintenance therapy on the prognosis of post-operative endometrial cancer patients with non-specific molecular profile.
The molecular classification of non-specific molecular profile (NSMP) is the most common type of endometrial cancer. Reducing the recurrence rate and improving the survival rate in patients with NSMP can effectively improve the overall prognosis of endometrial cancer.
NSMP endometrial cancers are featured as high sensitivity to hormones, which could be a potential target to improve the prognosis. Antiestrogenic therapy might be an effective treatment to improve the prognosis of NSMP endometrial cancer with high risk of recurrence and metastasis.
Letrozole, an oral non-steroidal aromatase inhibitor, might have positive impact on those patients as maintenance therapy after first-line postoperative adjuvant treatments. The current standardized treatment for intermediate-high risk endometrial cancer patients after chemotherapy and radiotherapy includes none but observation alone. However, with little adverse effects, low cost and easy availability, the practice of letrozole in hormonally-responsive breast cancer after surgery added to evidence to have an improvement in the prognosis in intermediate-high risk endometrial cancer. Thus, it is necessary to carry out a randomized trial to investigate the role of letrozole as maintenance therapy after postoperative adjuvant treatment in the prognosis of intermediate-high risk endometrial cancer.
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.
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 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Older than 18 years old;
- •Initial diagnosed with stage I-IV(FIGO2009) endometrial epithelial cancer, regardless of pathological types;
- •Surgery must have included a hysterectomy, bilateral salpingo-oophorectomy and sentinel node biopsy; pelvic lymph node sampling and para-aortic lymph node sampling are optional;
- •Life expectancy of 2 or more years.
- •Confirmed NSMP with intermediate or higher prognostic risk according to post-operative clinical pathological assessment and molecular classification;
- •Intermediate prognostic risk group:
- •Stage lB endometrioid + Iow-grade* + LVSI negative or focal
- •Stage IA endometrioid + high-grade*+ LVSI negative or focal
- •Stage IA non-endometrioid (serous, clear cell, undifferentiated carcinoma, carcinosarcoma, mixed) without myometrial invasion
- •High-intermediate prognostic risk group:
- •Stage I endometrioid + substantial LVSI, regardless of grade and depth of invasion
- •Stage lB endometrioid high-grade*, regardless of LVSI status
- •High prognostic risk group:
- •Stage Ill-IVA with no residual disease
- •Stage I-IVA non-endometrioid (serous, clear cell, undifferentiated carcinoma, carcinosarcoma, mixed) with myometrial invasion, and with no residual disease
- •Advanced Metastatic:
- •Stage III-IVA with residual disease
- •Stage IVB Low grade: G1-2; High grade:G3;
- •Received conventional adjuvant therapy after surgery according to the latest version of NCCN or ESGO/ESTRO/ESP guidelines;
- •Patients with residual tumor after surgery (any single site) must have achieved complete response or partial response after post-operative adjuvant therapy;
- •Expected start of letrozole maintenance within 3 months after adjuvant therapy;
- •Adequate organ function as defined by the following criteria:
- •White blood cell (WBC) ≥ 3000/μL or Absolute neutrophil count (ANC) ≥1500/μL
- •Platelets ≥100,000/μL
- •Serum Aspartate transaminase (AST) and/or serum alanine transaminase (ALT) ≤ 2 times upper limit of normal (ULN)
- •Serum creatinine ≤2 times ULN
- •Karnofsky score ≥60;
- •Eastern Cooperative Oncology Group (ECOG) Performance status ≤2;
- •Ability to take anti-thyroid drugs, calcium, vitamin D or bisphosphonates together.
排除标准
- •Endometrial stromal tumor;
- •Recurrent endometrial cancers;
- •Patients with low prognostic risk according to post-operative clinical pathological assessment ( Stage IA endometrioid + low-grade* +LVSI negative or focal);
- •Patients require no adjuvant therapy after surgery;
- •Negative expression in estrogen receptor or progesterone receptor according to post-operative Immunohistochemistry;
- •Received other adjuvant therapy within 6 months before surgery: including neoadjuvant therapy, hormone therapy, targeted therapy, immunotherapy and biotherapy, etc;
- •Patients with contraindications for letrozole;
- •Patients with other malignant tumors;
- •History of vital organ transplantation;
- •History of immune disease and need to take immunosuppressor;
- •Uncontrolled psychiatric illness or other situations that would limit compliance with study requirements;
- •History of drug abuse;
- •Participated in other clinical trials;
- •No ability or intention to receive letrozole maintenance/sign the consent/obey the study requirements.
研究组 & 干预措施
Letrozole
Letrozole 0.5mg qd po for 2 years after postoperative adjuvant therapy
干预措施: Letrozole 2.5mg (Drug)
结局指标
主要结局
the 3-year Progression-Free-Survival(PFS)
时间窗: 3 years
The percentage of patients who have first relapse within 3 years after surgery
次要结局
- Incidence of adverse events(From date of recruitment, assessed up to 5 years)
- Quality of life change(baseline, 1 year, and 2 years)
- Site of recurrence(8 years)
- the 3-year Overall survival(OS)(3 years)
- the 5-year PFS and OS(5 years)
研究者
Xiaojun Chen
Vice President of Obstetrics and Gynecology Hospital of Fudan University
Fudan University