Utero-ovarian Transposition in Patients With Pelvic Malignancies Undergoing Whole Pelvic Radiotherapy

N/ARecruitingNCT07419490

University of South Florida26 enrolled

Overview

This study is designed as a Phase I clinical trial enrolling female patients aged 18-40 years who have been diagnosed with pelvic malignancies requiring whole pelvic external radiation therapy (WPXRT) and who express interest in preserving fertility and ovarian function. The trial's primary objective is to assess the feasibility and safety of uterine and ovarian transposition (UOT). Premenopausal women under the age of 40 will undergo UOT using a novel minimally invasive approach. Feasibility and safety will be evaluated through standardized postoperative assessments, including: (A) success in mobilizing and repositioning the uterus, ovaries, and fallopian tubes while maintaining vascular integrity; (B) documentation of surgical complications; (C) monitoring the timeliness and adherence to planned WPXRT. To enhance safety and optimize outcomes, intraoperative imaging with indocyanine green fluorescence and Doppler ultrasonography will be employed. Short-term success will be defined by technical success in repositioning the uterus and ovaries with preserved vascular integrity, absence of major surgical complications, and timely initiation and completion of WPXRT. Long-term success will be evaluated by the preservation of fertility. The study's primary objective is also to evaluate surgical, reproductive, and quality-of-life outcomes following UOT. This objective will determine the procedure's efficacy in preserving ovarian and menstrual function and its potential to support future pregnancies. Endpoints include: (A) maintenance of normal premenopausal levels of FSH, LH, AMH, and estradiol at defined postoperative intervals; (B) assessment of menstrual timing, regularity, and characteristics to document return of ovulatory cycles; (C) evaluation of uterine integrity and reproductive potential using pelvic ultrasonography; (D) comprehensive evaluation of patient quality of life encompassing physical, emotional, sexual, and reproductive well-being. These measures will inform optimization of surgical techniques and provide a foundation for scaling the procedure to a broader population in future studies.

This is a phase I study aimed to evaluate feasibility and safety of utero-ovarian transposition (UOT) in young women undergoing whole pelvic radiation therapy (WPXRT) for treatment of a colorectal or other cancers localized to the pelvis. By comprehensively evaluating real-world outcomes for women undergoing this procedure, the proposed work will lay the groundwork necessary to establish UOT as a viable option for fertility preservation and survivorship for this unique patient population. Rigorous inclusion and exclusion criteria will ensure the selection of appropriate candidates, who will undergo a minimally invasive transposition of their cervix, uterus, tube and ovaries outside the planned radiation fields, thus sparing transposed organs from radiation exposure. Following a brief recovery, the radiation oncology team will proceed with WPXRT to treat each patient's cancer. If chemotherapy is indicated, it will be completed at this time, prior to the second procedure. After completing radiation therapy and/or chemotherapy, the uterus and adnexa will be surgically returned to their normal anatomical position. This study will assess surgical outcomes for enrolled subjects undergoing this care plan, assess quality of life and the preservation of fertility and uterine receptivity by multiple objective measures. Throughout the study, patients will be closely monitored for perioperative outcomes, including surgical complications, hospital stay, and quality of life. Patterns of menstruation, as well as levels of key hormones routinely used to assess fertility (FSH, LH, AMH, and estradiol) will be measured at key time points. Successful UOT will be defined as the ability to complete the procedure and successfully restore a viable uterus and adnexa capable of supporting normal menstruation and fertility post-radiation therapy. The resumption of menstrual cycles for six months following the procedure will be evaluated. Quality of life will be evaluated at multiple steps as women undergo the proposed procedures as well as throughout the planned 6 months follow up window. Data generated by this pilot study will provide critical insights into the feasibility, safety, and potential benefits of UOT as a fertility-preserving and ovarian function-conserving option for patients with pelvic malignancies undergoing WPXRT. Moving forward, data from this study will be used not only to build out the programmatic and clinical infrastructure needed to further evaluate the efficacy of UOT, but also to overcome roadblocks to its successful clinical implementation in the future.

Eligibility

Sex: FEMALEMin age: 18 MonthsMax age: 40 Months

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age: Women 18 - 40 years of age who wish to preserve their fertility. 2. Malignancy: Diagnosis of pelvic malignancies that require radiotherapy, including: 1. Colon and rectal cancer with tumors. 2. Anal cancer. 3. Other pelvic malignancies that require administration of WPXRT. 3. Desire for Fertility Preservation: The patient expresses a clear desire to preserve fertility and the ability to carry a pregnancy in the future. 4. Preoperative Ovarian Function: The patient must have normal ovarian function, demonstrated by specific hormonal values, including: 1. Follicle-Stimulating Hormone (FSH): \<10 IU/L 2. Luteinizing Hormone (LH): within normal reference range for reproductive age (typically 1.5-8 IU/L in the early follicular phase). 3. Anti-Müllerian Hormone (AMH): \>1 ng/mL 4. Estradiol (E2): within the normal range for the follicular phase (usually 30-120 pg/mL). 5. No Distant Metastasis: Absence of metastatic disease confirmed by imaging (CT, MRI, or PET scans). 6. Body Mass Index (BMI) \< 35. 7. Signed Informed Consent. Exclusion Criteria: 1. Advanced Cancer Stage: Patients with locally advanced or metastatic disease. 2. Significant Uterine Pathology: Presence of large uterine fibroids, adenomyosis, or other intrauterine pathologies that would complicate the procedure or future pregnancy. 3. Poor General Health or Comorbidities: Severe medical conditions that contraindicate surgical intervention, that include but not limited to: * Cardiovascular Disease: 1. Recent (within 6 months) myocardial infarction (MI). 2. Ejection fraction (EF): EF \<30%. 3. Uncontrolled hypertension: Systolic BP \>180 mmHg or Diastolic BP \>110 mmHg prior to surgery. 4. Severe aortic stenosis: Valve area \<1 cm² with symptomatic status. * Uncontrolled Diabetes Mellitus: 1. Hemoglobin A1c (HbA1c) \> 9% 2. Persistent fasting glucose \>250 mg/dL preoperatively despite optimization. * Severe Respiratory Diseases: 1. Forced expiratory volume (FEV1): \<50%. 2. Oxygen saturation: Resting SpO₂ \<88% on room air without supplemental oxygen. 3. CO2 retention: PaCO₂ \>50 mmHg. * Connective Tissue Disorders: 1. Severe systemic lupus erythematosus (SLE): Active lupus nephritis with GFR \<30 mL/min. 2. Scleroderma with severe pulmonary hypertension or FVC \<50% predicted. 3. Rheumatoid arthritis with severe cervical spine instability (atlantoaxial subluxation). * Severe Inflammatory Bowel Disease (IBD): 1. Severe Crohn's or ulcerative colitis flares with C-reactive protein (CRP) \>10 mg/L and hypoalbuminemia (Albumin \<2.5 g/dL). 2. Severe malnutrition: BMI \<18.5 kg/m² or Prealbumin \<10 mg/dL * Steroid dependency: 1. Chronic steroid use (\>20 mg prednisone daily) with no feasible taper pre-surgery. 4. Prior Pelvic Radiotherapy. 5. Prior history of systemic chemotherapy and immunotherapy that resulted in significant toxicity and residual deficit. 6. Pregnancy: Patients who are currently pregnant are excluded from consideration for uterine transposition. 7. Unsuitable for Ovarian Function Preservation: Women with signs of poor ovarian reserve, including: * FSH: \>10 IU/L * AMH: \<1 ng/mL * Estradiol: outside normal range. 8. Non-Candidate for Fertility: Patients with contraindications to future pregnancy, such as severe uterine abnormalities or significant risk for pregnancy-related complications. 9. Body Mass Index (BMI) ≥35. 10. Absence of One of the Gonadal Vessels. 11. Other unlisted conditions or diagnoses that, in the opinion of the primary investigator, render the patient an unsuitable candidate for uteroovarian transposition.

Outcomes

Primary Outcomes

Success of uterine transposition

Success of uterine transposition (feasibility) will be defined as the percentage of cases in which the uterus, ovaries, and fallopian tubes are successfully mobilized and repositioned as planned without the need for intraoperative conversion. Unit of Measure: Percentage of participants (%) Time Frame: up 30 days postsurgery.

Time frame: From enrollment to completion of surveillance/monitoring at 52 weeks

Secondary Outcomes

Postoperative Complications

Postoperative complications will be monitored. All complications will be graded according to the Clavien-Dindo classification system. Unit of Measure: Number of participants with complications.

Time frame: From enrollment to 4 weeks postsurgery

Menstrual Function

Menstrual function will be evaluated by assessing the return of menses, cycle regularity, and ovulatory characteristics through a standardized postoperative questionnaire. Unit of Measure: Percentage of participants (%)