Clinical trial NCT04362046: Fertility Sparing Management of EndomeTrial Cancer and Hyperplasia
Official title: Fertility Preservation Using Endomyometrial Resection for Atypical Hyperplasia and Low Grade, Stage 1A, Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endometrial Hyperplasia
Endometrial Cancer
Gynecologic Cancer
Keywords: Fertility preservation
Hysteroscopic uterine resection
High-dose progesterone
Lead sponsor: Vancouver Coastal Health Research Institute
Sponsor class: OTHER
Collaborators: name: University of British Columbia
First posted: 2020-04-24
Enrollment: 30
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study protocol evaluates the use of hysteroscopic endomyometrial resection in women diagnosed with atypical endometrial hyperplasia or grade I endometrial cancer who have not responded to anti-hormone therapy. Patients in this study wish to preserve fertility.

Detailed description: Endometrial cancer (EC) is the most common gynecological cancer among Canadian women. This cancer often arises from a precursor lesion called atypical endometrial hyperplasia (AH). Hysterectomy is the most effective treatment for EC and AH. It is well recognized that EC may be diagnosed in younger women of child-bearing age. The diagnosis of EC or AH in these younger women is devastating as a hysterectomy is frequently required. Though some of these women respond to high-dose progestin treatment, the failure rate is high (60%), necessitating surgery. Recent case series show that some women with AH and early EC can be treated by resecting the precursor lesion of the early cancerous area in the uterus by hysteroscopy without the need for hysterectomy. The fertility-sparing approach is outlined in this research protocol.This is a multidisciplinary research project with input from gynaecologic oncology, general gynaecology, reproductive endocrinology and infertility, and pathology. Our hypothesis is that hysteroscopic resection (HR) is a safe and effective treatment for AH or EC in women who want to preserve their fertility and have not been successfully treated using progestin therapy. Patients will be closely monitored to ensure that this is a safe and effective treatment option.

Eligibility criteria: All candidates for this protocol must have an adequate trial of anti-hormone therapy prior to hysteroscopic resection. In cases of EC, the minimum trial is 6 months of high-dose progestin. In cases of AH, being that this is a benign condition (pre-malignant), patients may not require a full 6 months of anti-hormone therapy. All patients must have a pre-HR hysteroscopic evaluation to confirm that they are suitable candidates for this study. Patients being considered for the experimental intervention (hysteroscopic resection) will be reviewed and discussed by the study committee in order to ensure that the following criterion are met in order to proceed with the surgical resection:

Inclusion criteria:

* Age less than 40 years
* Pathologist confirmed biopsy evidence of one of the following:

  1. Grade I endometrial endometrioid adrenocarcinoma (EC) with less than 1/3 of the endometrial surface involved.
  2. Atypical endometrial hyperplasia (AH)
* MRI demonstrating less than 1/3 myometrial invasion if the patient has EC
* Absence of significant surgical co-morbidities e.g. pulmonary hypertension, significant cardiac valvular disease, or contraindication to surgery.
* Desire to preserve fertility
* Reasonable chance to conceive based on consultation with an infertility specialist
* Adequate dose and duration of progesterone therapy prior to enrolment:
* Adequate dose:

  1. Medroxyprogesterone acetate (Provera; 200mg/day)
  2. Megestrol acetate (Megace; 160mg/day)
* Adequate duration: 6 months
* Failure of progestin therapy defined as:

  1. Unsuccessful eradication of hyperplasia or cancer in the uterus
  2. Intolerance to the side effects
* Signed informed consent

Exclusion criteria:

* Age 40 years and over
* Grade 2 or 3 endometrioid endometrial adenocarcinoma or non-endometrioid pathology
* Greater than 1/3 involvement of the endometrial surface in patients with Grade I EC
* Women who are not able to provide informed consent
* Women without pathologic confirmation of low-grade endometrioid carcinoma or AH
* Myometrial invasion on MRI greater than 1/3 total myometrial thickness.
* MRI evidence of ovarian or adnexal involvement
* The diagnosis of another cancer or medical condition that would interfere with the assessment of the hysteroscopic surgery success rates.
* Significant underlying fertility impairment that would significantly interfere with the success rate of HR

Primary outcomes:
measure: Conception rate of women attempting pregnancy
timeFrame: 3 years post-resection
measure: Overall conception rate
timeFrame: 3 years post-resection
measure: Local disease control rate (short-term failure of hysteroscopic resection)
timeFrame: 3 months post-resection
measure: Distant disease control rate (long-term failure of hysteroscopic resection)
timeFrame: 3 years post-resection
Secondary outcomes:
measure: Complications/side-effects
timeFrame: 3 years post-resection
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
Study officials:
affiliation: Vancouver Coastal Health
name: Mark Carey, MD
role: PRINCIPAL_INVESTIGATOR
References: