GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Cancer Patients

Obesity Clinical Trial

Official title:

Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Obese Progestin-insensitive Early-stage Endometrial Cancer Patients With Conservative Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06379113
• Other study ID #: 53211030-2
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 13, 2022
• Est. completion date: March 30, 2025

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: Xiaojun Chen, PhD
• Phone: 8602133189900
• Email: cxjlhjj[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the efficacy of GnRHa plus letrozole in obese progestin-insensitive EEC patients.

Description:

There were more and more women with early endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (EAH) who want to preserve fertility. Approximately 70% to 80% of females who meet the criteria for conservation treatment are able to achieve CR after progestin therapy, with a median time of 6-7 months, but about 20% to 30% of patients get no response or need to take longer time to achieve remission (over one year). With long duration of treatment, there will be more side effects such as weight gain, impaired liver function, endometrial injury, ovarian reserve inhibition etc. which will decrease the efficacy of conservative treatment. Previous researches had shown that GnRHa plus letrozole could be a better second-line treatment for obese progestin-insensitive patients. Till now, no similar studies were found, so we design this study to explore the efficacy of GnRHa plus letrozole in obese progestin-insensitive EEC and EAH patients to provide new evidences for improving conservative treatment efficacy. We defined obese patients as these with BMI ≥ 30kg/m2. This will be a single-centred prospective pilot study. Patients diagnosed as obese progestin-insensitive EEC by dilatation and curettage (D&C) or hysteroscopy will be enrolled. The primary endpoint is cumulative complete response (CR) rate at 28 weeks of treatment. The secondary endpoints include adverse events, duration of complete response, recurrent rate, pregnancy rate and quality of life of patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: March 30, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Have a confirmed initial pathological diagnosis based upon hysteroscopy:

histologically prove well-differentiated EEC G1 without myometrial invasion

• BMI=30kg/m2
• No signs of suspicious extrauterine involvement on enhanced magnetic resonance imaging (MRI) or enhanced computed tomography (CT) or ultrasound
• Using progestin, any of the following therapy, as first-line treatment:

1. Megestrol acetate = 160 mg qd using, combined with Levonorgestrel Lntrauterine System (LNG-IUS) inserted or not

2. Medroxyprogesterone acetate = 250 mg qd using, combined with LNG-IUS inserted or not

3. LNG-IUS inserted

• Progestin-insensitive:

1. remained with stable disease after 7 months of progestin use

2. did not achieve CR after 10 months of progestin use

• Have a desire for remaining reproductive function or uterus
• Good compliance with adjunctive treatment and follow-up

Exclusion Criteria:

• Combined with severe medical disease or severely impaired liver and kidney function
• Pathologically confirmed as endometrial cancer with suspicious myometrial invasion or extrauterine metastasis
• Patients with other types of endometrial cancer or other malignant tumors of the reproductive system
• Patients with breast cancer or other hormone- dependent tumors or diseases that cannot be used with GnRHa or Letrozole
• Strong request for uterine removal or other conservative treatment
• Known or suspected pregnancy
• Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
• Smoker(>15 cigarettes a day)

Related Conditions & MeSH terms

• Atypical Endometrial Hyperplasia
• Endometrial Hyperplasia
• Endometrial Neoplasms
• Hyperplasia
• Obesity
• Progesterone Resistance

Intervention

Drug:
• GnRH antagonist
Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks, and the maximum treatment courses will be 6. If the patient get CR within 6 courses, another 2 courses will be used as consolidation therapy.
• Letrozole 2.5mg
2.5mg po qd.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Xiaojun Chen

Country where clinical trial is conducted

China, 

References & Publications (1)

Zhou S, Xu Z, Yang B, Guan J, Shan W, Shi Y, Chen X. Characteristics of progestin-insensitive early stage endometrial cancer and atypical hyperplasia patients receiving second-line fertility-sparing treatment. J Gynecol Oncol. 2021 Jul;32(4):e57. doi: 10.3802/jgo.2021.32.e57. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rates within 28 weeks of treatment	The cumulative 28-week CR rates will be calculated in two groups. Patients will be evaluated with an hysteroscopy every 12 to 16 weeks. For some may delay the evaluation as personal reasons, we define the primary outcome measure as complete response rates within 28 weeks of treatment.	Up to 28 weeks
Secondary	Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be recorded, as well as incidence of adverse events.	Through study completion, an average of 28 weeks
Secondary	Time to achieve complete response	The median CR time will be calculated.	Up to 28 weeks
Secondary	Relapse rates		Through study completion, an average of 2 years
Secondary	Rates of fertility outcomes		Through study completion, an average of 2 years
Secondary	Compliance	Data on treatment and hysteroscopy management will be collected, and deviations from study protocol will be recorded in writing. For example, the time of drug interruptions due to related toxicities or AEs, and delay of hysteroscopy for personal reasons.	Through study completion, an average of 28 weeks