Bariatric Surgery for Endometrial Cancer

(B-FiERCE Trial)

Overseen By Tara Zad

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Progestin

Must not be taking: Weight loss medication

Disqualifiers: Myometrial invasion, High grade cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 15 months

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using weight loss medication.

What data supports the effectiveness of bariatric surgery as a treatment for endometrial cancer?

Bariatric surgery can help patients with extreme obesity lose weight rapidly, making them eligible for further cancer treatments like surgery. Studies suggest that bariatric surgery reduces the risk of developing endometrial cancer and can improve outcomes when combined with other treatments. ^{1 2 3 4 5}

Is bariatric surgery generally safe for humans?

Bariatric surgery, including procedures like the duodenal switch, is generally effective for weight loss but can have risks such as vitamin deficiencies, bleeding, and nutritional issues. It's important to have regular follow-ups and nutritional supplements to manage these risks. ^{6 7 8 9 10}

How does bariatric surgery differ from other treatments for endometrial cancer?

Bariatric surgery is unique for endometrial cancer treatment because it helps patients lose significant weight, making them eligible for further cancer treatments like surgery. This approach is particularly beneficial for patients with extreme obesity, where traditional weight loss methods have failed, and it may also reduce the overall risk of developing endometrial cancer. ^{1 2 3 4 5}

Research Team

Sarah E Ferguson, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for young women with obesity who have early-stage endometrial cancer or atypical hyperplasia, want to preserve their fertility, and have a BMI ≥ 35. They should not be pregnant, have no history of certain cancers or major upper abdominal surgery (except some procedures like appendectomy), and must understand the consent process.

Inclusion Criteria

Your body mass index (BMI) is 35 or higher.

I can do all my daily activities without help.

My cancer is in stage 1 and has not spread beyond the uterus.

Exclusion Criteria

My cancer has spread beyond the uterus, as shown by scans.

I had cancer before, but it was cured and I've been cancer-free for over 5 years.

I have a health condition that affects how my organs work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

21 months

Treatment

Participants are randomized to receive either bariatric surgery plus progestin intrauterine device or progestin intrauterine device alone

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of complete response rate and recurrence

6 years

Completion of Bariatric Surgery

Proportion of patients who complete bariatric surgery within 3-4 months of randomization

3-4 months

Treatment Details

Interventions

• Bariatric Surgery

Trial Overview The study tests if bariatric surgery combined with progestin therapy can help achieve significant weight loss and improve treatment response in obese women with early-stage endometrial cancer/atypical hyperplasia wishing to maintain fertility.

Participant Groups

Group I: Bariatric Surgery and Progestin Intrauterine Device Experimental Treatment 1 Intervention

This group will receive a progestin intrauterine device and be offered to undergo bariatric surgery.

Group II: Progestin Intrauterine Device Alone Active Control 1 Intervention

This group will receive a progestin intrauterine device alone.

Bariatric Surgery is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Bariatric Surgery for:

• Severe obesity (BMI ≥35 kg/m2) with comorbidities
• Type 2 diabetes
• Hypertension
• Sleep apnea
• High-risk cardiovascular disease

Approved in United States as Bariatric Surgery for:

• Severe obesity (BMI ≥35 kg/m2) with comorbidities
• Type 2 diabetes
• Hypertension
• Sleep apnea
• High-risk cardiovascular disease

Approved in Canada as Bariatric Surgery for:

• Severe obesity (BMI ≥35 kg/m2) with comorbidities
• Type 2 diabetes
• Hypertension
• Sleep apnea
• High-risk cardiovascular disease

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

A 17-year-old girl with obesity, type 2 diabetes, and early-stage endometrial cancer underwent laparoscopic sleeve gastrectomy, leading to significant weight loss and complete response to fertility-preserving treatment.

This case suggests that bariatric surgery may enhance the effectiveness of local progestin therapy in treating endometrial cancer while preserving fertility, marking a potential new approach for similar patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bariatric Surgery: Does It Play a Role in Fertility-Preserving Treatment Among Obese Young Women With Endometrial Cancer? Benito, V., López-Tomassetti, E., Esparza, M., et al.[2019]

Bariatric surgery significantly reduces the risk of developing endometrial cancer in women with obesity (BMI >30 kg/m²), based on a review of 23 relevant studies.

While there is strong evidence for risk reduction, there is limited research on the use of bariatric surgery as an additional treatment for existing endometrial cancer, highlighting a need for further investigation in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial cancer and bariatric surgery: A scoping review. Aubrey, C., Black, K., Campbell, S., et al.[2020]

Extreme obesity can prevent patients from undergoing primary surgical treatment for endometrial cancer, highlighting the need for alternative approaches.

Bariatric surgery is a safe and effective way to achieve rapid weight loss, making it a viable option for patients with extreme obesity to later undergo delayed hysterectomy for endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bariatric surgery after failed conservative management in a morbidly obese patient with endometrial cancer. Montemorano, L., Smrz, SA., Jalilvand, AD., et al.[2020]

Bariatric surgery effectively reduced the patient's BMI from 71.3 to 54.3 kg/m2, enabling her to qualify for necessary surgical treatment for early-stage endometrial cancer.

The total hysterectomy and bilateral salpingo-oophorectomy were successful with no complications, and follow-up assessments showed no evidence of cancer recurrence after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidly obese patient with endometrial cancer treated by bariatric surgery to enable cancer treatment. Sharma, N., Ragupathy, K.[2023]

Bariatric surgery appears to significantly reduce the risk of developing endometrial cancer, with only 0.4% of patients who underwent surgery developing the cancer compared to 1.4% in the control group, resulting in an odds ratio of 0.317.

The analysis was based on nine observational studies, including data from over 113,000 patients who had bariatric surgery, indicating a strong association but highlighting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Bariatric Surgery Affect the Incidence of Endometrial Cancer Development? A Systematic Review. Winder, AA., Kularatna, M., MacCormick, AD.[2019]

Duodenal switch (DS) surgery can be effective for weight loss in super obese patients, but it carries significant risks, including complications like duodenal stump blowout, which can lead to severe postoperative issues such as bleeding and abdominal pain.

Early diagnosis and appropriate management of duodenal stump leaks are crucial, involving stabilization of the patient and surgical repair, to prevent serious complications following the DS procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenal stump leak following a duodenal switch: A case report. Nelson, L., Moon, RC., Teixeira, AF., et al.[2020]

Increasing the common channel length to 200 cm in biliopancreatic diversion with duodenal switch (BPD-DS) resulted in similar weight loss outcomes compared to the standard 100 cm channel, with a follow-up of at least 3 years for 36 patients.

The 200 cm common channel was associated with a lower incidence of severe protein deficiency and hyperparathyroidism, suggesting it may reduce nutritional complications compared to the shorter channel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of duodenal switch with a 200-cm common channel: a matched, controlled trial. Lebel, S., Dion, G., Marceau, S., et al.[2022]

In a study of 65 patients followed for 5 years after duodenal switch surgery, the average excess body weight loss was 62%, demonstrating the procedure's effectiveness for long-term weight management.

The surgery also led to high remission rates for obesity-related conditions, with 96% of patients achieving remission from type 2 diabetes, 77% from hypertension, and 84% from dyslipidaemia, while post-operative nutritional deficiencies were lower than expected due to a comprehensive supplementation regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenal Switch Combined with Systematic Post-operative Supplementation and Regular Patient Follow-up Results in Good Nutritional Outcomes. Joret, MO., Nanayakkara, A., Kulasegaran, S., et al.[2022]

Biliopancreatic bypass with duodenal switch led to significant weight loss in patients, dropping from an average of 153.8 kg to 92.7 kg within one year, indicating its efficacy for treating morbid obesity.

However, the procedure is associated with a high risk of nutritional deficiencies and complications, particularly in patients with common channels shorter than 100 cm, suggesting that this surgery should be performed with caution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nutritional status after surgical treatment of obesity]. Tonstad, S., Sundfør, T., Myrvoll, EA.[2008]

Duodenal switch surgery resulted in significantly greater weight loss (mean reduction of 24.8 kg/m²) compared to gastric bypass (mean reduction of 17.3 kg/m²) over 2 years, indicating its superior efficacy for weight management in severely obese patients.

While both surgeries improved cardiovascular risk factors similarly, duodenal switch was associated with more adverse events, particularly related to malnutrition, highlighting the need for careful monitoring post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss, cardiovascular risk factors, and quality of life after gastric bypass and duodenal switch: a randomized trial. Søvik, TT., Aasheim, ET., Taha, O., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bariatric Surgery: Does It Play a Role in Fertility-Preserving Treatment Among Obese Young Women With Endometrial Cancer? [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Endometrial cancer and bariatric surgery: A scoping review. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Bariatric surgery after failed conservative management in a morbidly obese patient with endometrial cancer. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Morbidly obese patient with endometrial cancer treated by bariatric surgery to enable cancer treatment. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Does Bariatric Surgery Affect the Incidence of Endometrial Cancer Development? A Systematic Review. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Duodenal stump leak following a duodenal switch: A case report. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes of duodenal switch with a 200-cm common channel: a matched, controlled trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Duodenal Switch Combined with Systematic Post-operative Supplementation and Regular Patient Follow-up Results in Good Nutritional Outcomes. [2022]

9. Norway pubmed.ncbi.nlm.nih.gov

[Nutritional status after surgical treatment of obesity]. [2008]

10. United States pubmed.ncbi.nlm.nih.gov

Weight loss, cardiovascular risk factors, and quality of life after gastric bypass and duodenal switch: a randomized trial. [2018]