Clinical trial NCT04008563: Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
Official title: Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endometrial Cancer
Atypical Hyperplasia
Bariatric Surgery Candidate
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention Group: Bariatric Surgery and Progestin Intrauterine Device (pIUD) Non-Intervention Group: Progestin Intrauterine Device (pIUD) alone

Participants who consent will be randomized in a 1:1 allocation.
Primary purpose: TREATMENT

Brief summary: A growing population of young women with obesity are developing atypical hyperplasia (pre-cancer) and endometrial cancer. Progestin is the standard treatment for women who wish to preserve fertility, but this approach does not address the underlying cause of endometrial cancer/atypical hyperplasia (obesity); thus response rates are low and recurrence rates are high. Significant weight loss by bariatric surgery, in combination with progestin therapy may result in greater and more durable response rates.

Detailed description: The incidence of endometrial cancer is increasing at an alarming rate (2.6% per year). This trend parallels the rising rate of obesity, the most significant increasing risk factor for endometrial cancer. Young women with obesity and endometrial cancer or atypical hyperplasia who want to maintain their fertility and thus avoid hysterectomy are treated with progestin therapy, such as progestin intra-uterine device (pIUD). However, the pIUD achieves cancer regression in only 50-70% of women, and over 50% of initial responders will develop recurrence within two years. The effectiveness of the pIUD may be improved if the driver of endometrial cancer (obesity) was simultaneously addressed. Multiple epidemiologic studies have demonstrated that bariatric surgery reduces the risk of developing endometrial cancer. Our research aims to answer the question: "Is bariatric surgery in addition to the pIUD a feasible and acceptable option for young women with endometrial cancer/atypical hyperplasia who wish to maintain their childbearing potential compared to standard treatment of pIUD alone?

This is a pilot randomized controlled trial to assess the feasibility of a full-scale randomized controlled trial. Eligible women will be identified and consented over a 21-month period, and participants will be randomized to bariatric surgery plus standard pIUD (intervention group) or to standard pIUD alone (non-intervention group) in a 1:1 fashion.

Eligibility criteria: Inclusion Criteria:

* BMI ≥ 35
* Diagnosis of grade 1 endometrioid endometrial cancer or complex atypical hyperplasia
* Clinical stage 1 disease - no evidence of metastatic disease beyond the uterus by imaging performed (MRI, CT)
* ECOG status \<2
* Desire for fertility preservation
* No contraindications to progestin intrauterine device (IUD)
* Have signed an approved informed consent form

Exclusion Criteria:

* Evidence of myometrial invasion or extra-uterine disease on imaging
* High grade or p53 endometrial cancer
* History of other malignancies, except if curatively treated with no evidence of disease for \> 5 years
* Previous major upper abdominal surgery (ex. previous bariatric surgery, splenectomy, partial gastrectomy, liver resection, bowel resection). Appendectomy, cholecystectomy, hernia repair, and caesarean section are acceptable procedures for inclusion.
* Current use of weight loss medication. NB: patients taking glucagon-like peptide 1 (GLP-1) agonists (e.g., OZEMPIC) for the treatment of diabetes will not be excluded.
* Contraindications to sleeve gastrectomy
* Medical co-morbidity with end-organ dysfunction
* Unable to understand and participate in the informed consent process
* Currently pregnant
* Active smoking in ≤6 months
* Active substance use disorder
* Current untreated or severe psychiatric issue

Primary outcomes:
measure: Recruitment Rate
timeFrame: Year 5
Secondary outcomes:
measure: Completion of Bariatric Surgery
timeFrame: Year 5
measure: Loss to Follow-Up Rate
timeFrame: Year 6
measure: Completion of Patient Reported Outcome Questionnaires
timeFrame: Year 5
measure: Complete Response Rate
timeFrame: Year 6
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Sarah E Ferguson, MD
role: PRINCIPAL_INVESTIGATOR
References: