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

Cervical Cancer Clinical Trial

— FUSIONIV  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02986568
• Other study ID #: 2015-1616
• Status: Recruiting
• Phase: N/A
• Start date: May 10, 2016
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2020
• Source: Seoul National University Hospital
• Contact: Hee Seung Kim, MD
• Phone: 82-2-2072-4863
• Email: bboddi0311[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cancer
• Uterine Neoplasms

Intervention

Procedure:
• Cervical cancer
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.
• Uterine cancer
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.
• Cervical cancer, pelvic sidewall invasion
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.
• Non-cervical cancer, pelvic sidewall invasion
Perform Fusion Laterally extended endopelvic resection (LEER). After surgery, appropriate adjuvant chemotherapy will be administered depending on the tumor type.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (16)

Chi DS, Franklin CC, Levine DA, Akselrod F, Sabbatini P, Jarnagin WR, DeMatteo R, Poynor EA, Abu-Rustum NR, Barakat RR. Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach. Gynecol Oncol. 2004 Sep;94(3):650-4. — View Citation

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. — View Citation

Fujii S. Anatomic identification of nerve-sparing radical hysterectomy: a step-by-step procedure. Gynecol Oncol. 2008 Nov;111(2 Suppl):S33-41. doi: 10.1016/j.ygyno.2008.07.026. Epub 2008 Aug 27. — View Citation

Höckel M, Hentschel B, Horn LC. Association between developmental steps in the organogenesis of the uterine cervix and locoregional progression of cervical cancer: a prospective clinicopathological analysis. Lancet Oncol. 2014 Apr;15(4):445-56. doi: 10.1016/S1470-2045(14)70060-9. Epub 2014 Mar 19. — View Citation

Höckel M, Horn LC, Einenkel J. (Laterally) extended endopelvic resection: surgical treatment of locally advanced and recurrent cancer of the uterine cervix and vagina based on ontogenetic anatomy. Gynecol Oncol. 2012 Nov;127(2):297-302. doi: 10.1016/j.ygyno.2012.07.120. Epub 2012 Aug 1. — View Citation

Höckel M, Horn LC, Fritsch H. Association between the mesenchymal compartment of uterovaginal organogenesis and local tumour spread in stage IB-IIB cervical carcinoma: a prospective study. Lancet Oncol. 2005 Oct;6(10):751-6. Epub 2005 Sep 8. — View Citation

Höckel M, Horn LC, Manthey N, Braumann UD, Wolf U, Teichmann G, Frauenschläger K, Dornhöfer N, Einenkel J. Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis. Lancet Oncol. 2009 Jul;10(7):683-92. doi: 10.1016/S1470-2045(09)70100-7. Epub 2009 May 29. — View Citation

Höckel M. Laterally extended endopelvic resection. Novel surgical treatment of locally recurrent cervical carcinoma involving the pelvic side wall. Gynecol Oncol. 2003 Nov;91(2):369-77. — View Citation

Höckel M. Long-term experience with (laterally) extended endopelvic resection (LEER) in relapsed pelvic malignancies. Curr Oncol Rep. 2015 Mar;17(3):435. doi: 10.1007/s11912-014-0435-8. Review. — View Citation

Kim HS, Kim K, Ryoo SB, Seo JH, Kim SY, Park JW, Kim MA, Hong KS, Jeong CW, Song YS; FUSION Study Group. Conventional versus nerve-sparing radical surgery for cervical cancer: a meta-analysis. J Gynecol Oncol. 2015 Apr;26(2):100-10. doi: 10.3802/jgo.2015.26.2.100. — View Citation

Kim HS, Kim TH, Suh DH, Kim SY, Kim MA, Jeong CW, Hong KS, Song YS. Success Factors of Laparoscopic Nerve-sparing Radical Hysterectomy for Preserving Bladder Function in Patients with Cervical Cancer: A Protocol-Based Prospective Cohort Study. Ann Surg Oncol. 2015;22(6):1987-95. doi: 10.1245/s10434-014-4197-1. Epub 2014 Dec 3. — View Citation

Kimmig R, Aktas B, Buderath P, Wimberger P, Iannaccone A, Heubner M. Definition of compartment-based radical surgery in uterine cancer: modified radical hysterectomy in intermediate/high-risk endometrial cancer using peritoneal mesometrial resection (PMMR) by M Höckel translated to robotic surgery. World J Surg Oncol. 2013 Aug 16;11:198. doi: 10.1186/1477-7819-11-198. — View Citation

Koh WJ, Greer BE, Abu-Rustum NR, Apte SM, Campos SM, Chan J, Cho KR, Cohn D, Crispens MA, Dupont N, Eifel PJ, Fader AN, Fisher CM, Gaffney DK, George S, Han E, Huh WK, Lurain JR 3rd, Martin L, Mutch D, Remmenga SW, Reynolds RK, Small W Jr, Teng N, Tillmanns T, Valea FA, McMillian N, Hughes M. Uterine neoplasms, version 1.2014. J Natl Compr Canc Netw. 2014 Feb;12(2):248-80. — View Citation

Koh WJ, Greer BE, Abu-Rustum NR, Apte SM, Campos SM, Cho KR, Chu C, Cohn D, Crispens MA, Dorigo O, Eifel PJ, Fisher CM, Frederick P, Gaffney DK, Han E, Huh WK, Lurain JR 3rd, Mutch D, Fader AN, Remmenga SW, Reynolds RK, Teng N, Tillmanns T, Valea FA, Yashar CM, McMillian NR, Scavone JL. Cervical Cancer, Version 2.2015. J Natl Compr Canc Netw. 2015 Apr;13(4):395-404; quiz 404. — View Citation

Piver MS, Rutledge F, Smith JP. Five classes of extended hysterectomy for women with cervical cancer. Obstet Gynecol. 1974 Aug;44(2):265-72. — View Citation

Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol. 2008 Mar;9(3):297-303. doi: 10.1016/S1470-2045(08)70074-3. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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