Efficacy of the Standard Treatment and Fusion Ontogenetic Surgery for Gynecologic Cancers

Study Overview
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Brief Summary
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The purpose of this study is to compare standard treatment and fusion ontogenetic surgery (total mesometrial resection, laterally extended endopelvic resection, peritoneal mesometrial resection) for gynecologic cancer in order to evaluate treatment response, adverse effect and survival.

Detailed Description
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Fujii method and ontogenetic surgery are the surgical method of radical hysterectomy that can preserve pelvic organ function as much as possible. Fujii method has advantage of preserving pelvic autonomic nerve with radical resection of tissue under parametrium. And ontogenetic surgery has advantage of reducing need of radiation therapy by radical resection of tissue above parametrium. This study is prospective study for fusion ontogenetic surgery that has the advantage of both Fujji method and ontogenetic surgery.

Official Title
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Cohort Study for Comparing the Efficacy Between the Standard Treatment and Fusion Ontogenetic Surgery for Gynecologic Cancers (FUSION Trial IV)

Conditions
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Cervical Cancer, Uterine Cancer

Intervention / Treatment
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* Procedure: Cervical cancer
* Procedure: Uterine cancer
* Procedure: Cervical cancer, pelvic sidewall invasion
* Procedure: Non-cervical cancer, pelvic sidewall invasion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, Age ≥ 20 years Patients with primary, recurrent, or refractory cervical cancer (FIGO stage IB1-IVA), primary, recurrent, or refractory uterine cancer (FIGO stage IA, grade 3, IB-IVA), or gynecologic cancer patients showing pelvic sidewall recurrence. ECOG performance status 0 or 1 Extensive surgery might be expected to cure the disease, or expected to relieve severe pelvic pain. Patients who signed an approved informed consent Patients who do not have a treatment option other than surgery. Exclusion Criteria: Female, Age < 20 years ECOG performance status ≥2 Bilateral pelvic sidewall invasion Patients who had undergone radical hysterectomy, trachelectomy, or hysterectomy in case of the primary disease. Patients who refused to sign an informed consent

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervical cancer<br>Primary cervical cancer patients, FIGO stage IB1-IIB Refractory cervical cancer patients who do not respond to concurrent chemoradiotherapy or radiotherapy Recurrent cervical cancer after concurrent chemoradiotherapy or radiotherapy | Procedure: Cervical cancer<br>* If tumor sized ≥ 5cm, undergo neoadjuvant chemotherapy with Cisplatin before surgery. (40mg/m2 on day 1 of each 7 day cycle for 5 cycles), then perform Fusion TMMR after neoadjuvant chemotherapy with cisplatin as above. If tumor size < 5cm, perform Fusion Total mesometrial resection (TMMR) After surgery, if resection margin, more than two pelvic lymph node or more than one para-aortic lymph node is positive in pathologic report, undergo adjuvant chemotherapy. If not, no adjuvant therapy.<br>|
| Experimental: Uterine cancer<br>Primary uterine cancer patients, FIGO stage IA, grade3, IB-IVA Refractory uterine cancer who does not respond to concurrent chemoradiotherapy or radiotherapy Recurrent uterine cancer after concurrent chemoradiotherapy or radiotherapy | Procedure: Uterine cancer<br>* Perform Fusion Peritoneal mesometrial resection (PMMR). After surgery, if resection margin, more than two pelvic lymph node or more than one para-aortic lymph node is positive in pathologic report, undergo adjuvant chemotherapy. If not, no adjuvant therapy.<br>|
| Experimental: Cervical cancer, pelvic sidewall invasion<br>Cervical cancer patients showing pelvic sidewall invasion Primary cervical cancer Refractory cervical cancer patients who do not respond to concurrent chemoradiotherapy or radiotherapy Recurrent cervical cancer after concurrent chemoradiotherapy or radiotherapy | Procedure: Cervical cancer, pelvic sidewall invasion<br>* Perform Fusion Laterally extended endopelvic resection (LEER). After surgery, if resection margin, more than two pelvic lymph node or more than one para-aortic lymph node is positive in pathologic report, undergo adjuvant chemotherapy. Patients with primary disease will be treated with adjvuant chemotherapy. In case of recurrent disease, bevacizumab, paclitaxel, and cisplaitn will be administered regardless of the pathologic report (bevacizumab 15mg/kg on day 1, paclitaxel 135mg/m2 on day 1, and cisplatin 50mg/m2 on day 2, of each 21 day cycle). If not, no adjuvant therapy.<br>|
| Experimental: Non-cervical cancer, pelvic sidewall invasion<br>Gynecologic cancer patients other than cerivcal cancer, showing pelvic sidewall invasion with or without distant metastasis Patients showing uncontrolled pelvic pain due to the tumor invasion | Procedure: Non-cervical cancer, pelvic sidewall invasion<br>* Perform Fusion Laterally extended endopelvic resection (LEER). After surgery, appropriate adjuvant chemotherapy will be administered depending on the tumor type.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The time interval from treatment start date to disease recurrence or progression date | From date of treatment start until the date of first documented progression or date of death (by any cause, in the absence of disease progression) whichever came first, assessed up to 60 months | 
| Overall survival | the time interval from treatment start date to death or end of study date | From the date of treatment start until death due to any cause, assessed up to 60 months | 
| Treatment-free interval | The time interval from treatment end date to disease recurrence or progression date | From date of treatment end until the date of first documented progression or date of death (by any cause, in the absence of disease progression) whichever came first, assessed up to 60 months | 
| Treatment-related survival | the time interval from treatment start date to death or end of study date (recurrent or refractory disease) | the time interval from treatment start date to death or end of study date assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | Tumor response after surgery, and the evaluation is based on revised RECIST version 1.1 | 3 weeks after completion of ontogenetic surgery up to 6 weeks | 
| Postoperative complications 1 | Incidence of early complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System | after the ontogenetic surgery, up to 30 days | 
| Postoperative complications 2 | Incidence of late complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System | 31 days after the ontogenetic surgery through study completion, an average of 1 year | 
| Neurologic disturbance of low extremity | Incidence of motor and sensory disturbances of low extremities, and the grading is based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | after the ontogenetic surgery, up to 30 days | 
| Pain evaluation | Pelvic pain evaluated by numeric rating scale and morphine milligram equivalents (MME) | 1 day before the ontogenetic surgery, and at the time of discharge after postoperative management of the ontogenetic surgery assessed up to 60 months | 
| Time to normal bladder function | In case of bladder preservation, normal bladder function is evaluated by residual urine check after time voiding, and the volume of residual urine is less than 100cc. The time from the ontogentic surgery to the time of confirmation or normal bladder function. | The time from the ontogentic surgery to the time of confirmation or normal bladder function, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ontogenetic surgery, TMMR, PMMR, LEER