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出境医 / 临床实验 / Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium (B-FiERCE)

Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium (B-FiERCE)

Study Description
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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Atypical Hyperplasia Bariatric Surgery Candidate Procedure: Bariatric Surgery Not Applicable

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.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
Estimated Study Start Date : August 1, 2020
Estimated Primary Completion Date : August 1, 2023
Estimated Study Completion Date : August 1, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Bariatric Surgery and Progestin Intrauterine Device
This group will receive a progestin intrauterine device and be offered to undergo bariatric surgery.
Procedure: Bariatric Surgery
Patients who are randomized to the intervention group will receive a progestin intrauterine device and be referred for bariatric service to undergo bariatric surgery within 3 months of their study consent.

No Intervention: Progestin Intrauterine Device Alone
This group will receive a progestin intrauterine device alone.
Outcome Measures
Primary Outcome Measures :
  1. Recruitment Rate [ Time Frame: Year 3 ]
    To determine the proportion of eligible women who agree to participate in the study (recruitment rate). The primary outcome will be met and a full scale randomized controlled trial to assess efficacy will be conducted if ≥ 40% recruitment rate is achieved. Patients' reasons for participation or non-participation will be recorded.


Secondary Outcome Measures :
  1. Completion of Bariatric Surgery [ Time Frame: Year 3 ]
    Proportion of patients who complete bariatric surgery within 3 months of randomization. A rate of >85% will be considered feasible.

  2. Loss to Follow-Up Rate [ Time Frame: Year 3 ]
    Loss to follow-up rate, defined as proportion of patients who do not complete 15-month assessment. A loss to follow-up rate of <20% will be considered feasible.

  3. Completion of Patient Reported Outcome Questionnaires [ Time Frame: Year 3 ]
    Completion rate of patient reported outcomes that will be used in the full-scale randomized controlled trial. Completion of >80% of patient reported outcomes at baseline will indicate that use of these questionnaires is feasible.

  4. Complete Response Rate [ Time Frame: Year 3 ]
    Overall complete response rate (CRR) after treatment with progestin intrauterine device (pIUD). This study is not powered to detect an improvement in CRR in the intervention vs. non-intervention group. However, the proportion of women who obtain a complete response in the pIUD alone group at 15 months will be used as the baseline CRR for this population and will be used to derive a sample size for a full-scale randomized controlled trial. We believe that this will be more accurate than using published data retrospective studies that are not specific to women with obesity. We will also collect the following data: (a) time to complete response, (b) overall recurrence rate, and (c) time to recurrence.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 41 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 physical exam or 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
  • Evidence of adenomyosis seen on MRI
  • Previous major upper abdominal surgery (ex. 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
  • Contraindications to sleeve gastrectomy
  • Medical co-morbidity with end-organ dysfunction
  • Unable to understand and participate in the informed consent process
  • Currently pregnant
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Gabrielle Ene 416-946-4501 ext 3969 Gabrielle.Ene@uhnresearch.ca

Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Sarah E Ferguson, MD University Health Network, Toronto
Tracking Information
First Submitted Date  ICMJE July 3, 2019
First Posted Date  ICMJE July 5, 2019
Last Update Posted Date March 25, 2020
Estimated Study Start Date  ICMJE August 1, 2020
Estimated Primary Completion Date August 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
Recruitment Rate [ Time Frame: Year 3 ]
To determine the proportion of eligible women who agree to participate in the study (recruitment rate). The primary outcome will be met and a full scale randomized controlled trial to assess efficacy will be conducted if ≥ 40% recruitment rate is achieved. Patients' reasons for participation or non-participation will be recorded.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • Completion of Bariatric Surgery [ Time Frame: Year 3 ]
    Proportion of patients who complete bariatric surgery within 3 months of randomization. A rate of >85% will be considered feasible.
  • Loss to Follow-Up Rate [ Time Frame: Year 3 ]
    Loss to follow-up rate, defined as proportion of patients who do not complete 15-month assessment. A loss to follow-up rate of <20% will be considered feasible.
  • Completion of Patient Reported Outcome Questionnaires [ Time Frame: Year 3 ]
    Completion rate of patient reported outcomes that will be used in the full-scale randomized controlled trial. Completion of >80% of patient reported outcomes at baseline will indicate that use of these questionnaires is feasible.
  • Complete Response Rate [ Time Frame: Year 3 ]
    Overall complete response rate (CRR) after treatment with progestin intrauterine device (pIUD). This study is not powered to detect an improvement in CRR in the intervention vs. non-intervention group. However, the proportion of women who obtain a complete response in the pIUD alone group at 15 months will be used as the baseline CRR for this population and will be used to derive a sample size for a full-scale randomized controlled trial. We believe that this will be more accurate than using published data retrospective studies that are not specific to women with obesity. We will also collect the following data: (a) time to complete response, (b) overall recurrence rate, and (c) time to recurrence.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
Official Title  ICMJE Bariatric Surgery for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Endometrial Cancer
  • Atypical Hyperplasia
  • Bariatric Surgery Candidate
Intervention  ICMJE Procedure: Bariatric Surgery
Patients who are randomized to the intervention group will receive a progestin intrauterine device and be referred for bariatric service to undergo bariatric surgery within 3 months of their study consent.
Study Arms  ICMJE
  • Experimental: Bariatric Surgery and Progestin Intrauterine Device
    This group will receive a progestin intrauterine device and be offered to undergo bariatric surgery.
    Intervention: Procedure: Bariatric Surgery
  • No Intervention: Progestin Intrauterine Device Alone
    This group will receive a progestin intrauterine device alone.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2023
Estimated Primary Completion Date August 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 physical exam or 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
  • Evidence of adenomyosis seen on MRI
  • Previous major upper abdominal surgery (ex. 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
  • Contraindications to sleeve gastrectomy
  • Medical co-morbidity with end-organ dysfunction
  • Unable to understand and participate in the informed consent process
  • Currently pregnant
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 41 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gabrielle Ene 416-946-4501 ext 3969 Gabrielle.Ene@uhnresearch.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04008563
Other Study ID Numbers  ICMJE 19-5487
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sarah E Ferguson, MD University Health Network, Toronto
PRS Account University Health Network, Toronto
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP