GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Cancer Patients

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат Letrozole 2.5mg
  2.5mg po qd.

Первичные конечные точки

• Complete response rates within 28 weeks of treatment [Срок оценки: Up to 28 weeks]

Вторичные конечные точки (5)

• Adverse events [Срок оценки: Through study completion, an average of 28 weeks]
• Time to achieve complete response [Срок оценки: Up to 28 weeks]
• Relapse rates [Срок оценки: Through study completion, an average of 2 years]
• Rates of fertility outcomes [Срок оценки: Through study completion, an average of 2 years]
• Compliance [Срок оценки: Through study completion, an average of 28 weeks]

Критерии участия

Критерии включения

• 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:

• Megestrol acetate ≥ 160 mg qd using, combined with Levonorgestrel Lntrauterine System (LNG-IUS) inserted or not
• Medroxyprogesterone acetate ≥ 250 mg qd using, combined with LNG-IUS inserted or not
• LNG-IUS inserted
• Progestin-insensitive:

• remained with stable disease after 7 months of progestin use
• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Tenth People's Hospital of Tongji University — Шанхай
• Obstetrics and Gynecology Hospital, Fudan University — Шанхай

Публикации

• 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. PMID 34085795

Идентификаторы

NCT: NCT06379113 · 53211030-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗