Therapeutic Effect of Surgical Debulking of Metastatic Lymph Nodes in Cervical Cancer Stage IIICr

Cervical Cancer Clinical Trial

Official title:

Therapeutic Effect of Surgical Debulking of Metastatic Lymph Nodes in Cervical Cancer Stage IIICr: A Phase III, Randomized Controlled Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05421650
• Other study ID #: KGOG1047_DEBULK
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2022
• Est. completion date: March 31, 2029

Study information

• Verified date: February 2023
• Source: CHA University
• Contact: Ju-Won Roh
• Phone: +82-31-782-8312
• Email: rohjuwon[@]hanmail.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a prospective, multicenter and randomized clinical trial (DEBULK trial) to determine the therapeutic effect of surgical debulking of bulky or multiple lymph nodes before concurrent chemoradiation therapy (CCRT) in cervical cancer stage IIICr.

Description:

Bulky or multiple lymph nodes metastasis in cervical cancer shows poor prognosis and can also diminish the effect of radiotherapy or concurrent chemoradiation therapy (CCRT). However, it is difficult to increase the dose of radiation and chemotherapy considering their side effects. Therefore, the objective of this study is to determine the therapeutic effect of surgical debulking of bulky or multiple lymph nodes before concurrent chemoradiation therapy (CCRT) compared to CCRT only, in cervical cancer stage IIICr. This study is a phase III, multicenter and randomized clinical trial (DEBULK trial).

• Concurrent chemoradiation therapy (CCRT)

• Surgical debulking of bulky or multiple lymph node followed by CCRT

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 234
• Est. completion date: March 31, 2029
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 70 Years

Eligibility

1) Inclusion Criteria

1. Women =20 years and = 70 years of age

2. Cervical histopathology results of newly diagnosed squamous cell carcinoma, glandular epithelial cell, or adenosquamous carcinoma

3. When the radiology examinations such as CT, MRI, or PET-CT show the short-axis of the pelvic lymph node or paraaortic lymph node under the renal vein is = 2cm, or more than 3 lymph nodes with a short axis = 1 cm

4. When concurrent chemoradiation therapy is planned as a treatment for cervical cancer

5. Patient whose competency is ECOG performance score 0-1

6. A patient which has signed the approved informed consent form for study subjects

7. A patient for which it is determined that pre-surgical debulking is possible for lymph node metastasis as confirmed by radiological examination

2) Exclusion Criteria

1. A patient who has been diagnosed with cancer of any organ other than thyroid cancer (excluding stage 0 cancer) within the previous 5 years

2. A patient that is pregnant or plans to become pregnant during the clinical study period

3. A patient with any active infectious disease or incurable severe inflammation.

4. When surgery is not possible due to internal or surgical disease

5. When chemotherapy is impossible due to internal or surgical disease

6. Patient with a history of pelvic radiation therapy

7. Patient with a history of subtotal hysterectomy

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Radiation:
• CCRT
Radiation: Extended field-external beam radiation therapy (EF-EBRT) + brachytherapy + lymph node boost. Chemotherapy: Cisplatin 40mg/m2, every week, 4 to 6 cycles. Radiation and chemotherapy are administered concurrently.

Procedure:
• Surgical debulking of bulky or multiple lymph nodes
Open/minimally invasive method. Surgical debulking of bulky or multiple lymph nodes. Postoperative imaging evaluation to determine whether the lymph node has been successfully removed.

Radiation:
• CCRT
Radiation: EBRT/EF-EBRT + brachytherapy + lymph node boost. Chemotherapy: Cisplatin 40mg/m2, every week, 4 to 6 cycles. Radiation and chemotherapy are administered concurrently.

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu-si
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu-si
Korea, Republic of	Dongguk University Medical Center	Goyang-si	Gyeonggi-do
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Hanyang University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul ST. Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan	Gyeongsangbuk-do

Sponsors (17)

Lead Sponsor

Collaborator

CHA University

Asan Medical Center, DongGuk University, Ewha Womans University, Gachon University Gil Medical Center, Gangnam Severance Hospital, Hanyang University, Keimyung University Dongsan Medical Center, Korea University Ansan Hospital, Korean Gynecologic Oncology Group, Kyungpook National University Chilgok Hospital, National Cancer Center, Korea, Pusan National University Yangsan Hospital, Samsung Medical Center, Seoul National University Hospital, Seoul St. Mary's Hospital, Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (16)

Abu-Rustum NR, Yashar CM, Bean S, Bradley K, Campos SM, Chon HS, Chu C, Cohn D, Crispens MA, Damast S, Fisher CM, Frederick P, Gaffney DK, Giuntoli R, Han E, Huh WK, Lurain Iii JR, Mariani A, Mutch D, Nagel C, Nekhlyudov L, Fader AN, Remmenga SW, Reynolds RK, Sisodia R, Tillmanns T, Ueda S, Urban R, Wyse E, McMillian NR, Motter AD. NCCN Guidelines Insights: Cervical Cancer, Version 1.2020. J Natl Compr Canc Netw. 2020 Jun;18(6):660-666. doi: 10.6004/jnccn.2020.0027. — View Citation

Bhatla N, Berek JS, Cuello Fredes M, Denny LA, Grenman S, Karunaratne K, Kehoe ST, Konishi I, Olawaiye AB, Prat J, Sankaranarayanan R, Brierley J, Mutch D, Querleu D, Cibula D, Quinn M, Botha H, Sigurd L, Rice L, Ryu HS, Ngan H, Maenpaa J, Andrijono A, Purwoto G, Maheshwari A, Bafna UD, Plante M, Natarajan J. Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynaecol Obstet. 2019 Apr;145(1):129-135. doi: 10.1002/ijgo.12749. Epub 2019 Jan 17. Erratum In: Int J Gynaecol Obstet. 2019 Nov;147(2):279-280. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Jung KW, Won YJ, Kong HJ, Lee ES. Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2016. Cancer Res Treat. 2019 Apr;51(2):417-430. doi: 10.4143/crt.2019.138. Epub 2019 Mar 18. — View Citation

Lee M, Choi CH, Chun YK, Kim YH, Lee KB, Lee SW, Shim SH, Song YJ, Roh JW, Chang SJ, Lee JM. Surgical manual of the Korean Gynecologic Oncology Group: classification of hysterectomy and lymphadenectomy. J Gynecol Oncol. 2017 Jan;28(1):e5. doi: 10.3802/jgo.2017.28.e5. Epub 2016 Aug 19. — View Citation

Lim MC, Bae J, Park JY, Lim S, Kang S, Seo SS, Kim JY, Rho JW, Park SY. Experiences of pretreatment laparoscopic surgical staging in patients with locally advanced cervical cancer: results of a prospective study. J Gynecol Oncol. 2008 Jun;19(2):123-8. doi: 10.3802/jgo.2008.19.2.123. Epub 2008 Jun 20. — View Citation

Marnitz S, Kohler C, Roth C, Fuller J, Hinkelbein W, Schneider A. Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer? Gynecol Oncol. 2005 Dec;99(3):536-44. doi: 10.1016/j.ygyno.2005.07.005. Epub 2005 Aug 29. — View Citation

Oh J, Seol KH, Choi YS, Lee JW, Bae JY. Clinical significance of lymph node size in locally advanced cervical cancer treated with concurrent chemoradiotherapy. Yeungnam Univ J Med. 2019 May;36(2):115-123. doi: 10.12701/yujm.2019.00143. Epub 2019 Feb 21. — View Citation

Pedone Anchora L, Carbone V, Gallotta V, Fanfani F, Cosentino F, Turco LC, Fedele C, Bizzarri N, Scambia G, Ferrandina G. Should the Number of Metastatic Pelvic Lymph Nodes be Integrated into the 2018 Figo Staging Classification of Early Stage Cervical Cancer? Cancers (Basel). 2020 Jun 12;12(6):1552. doi: 10.3390/cancers12061552. — View Citation

Shin W, Ham TY, Park YR, Lim MC, Won YJ. Comparing survival outcomes for cervical cancer based on the 2014 and 2018 International Federation of Gynecology and Obstetrics staging systems. Sci Rep. 2021 Mar 26;11(1):6988. doi: 10.1038/s41598-021-86283-2. — View Citation

Song S, Kim JY, Kim YJ, Yoo HJ, Kim SH, Kim SK, Lim MC, Kang S, Seo SS, Park SY. The size of the metastatic lymph node is an independent prognostic factor for the patients with cervical cancer treated by definitive radiotherapy. Radiother Oncol. 2013 Jul;108(1):168-73. doi: 10.1016/j.radonc.2013.04.015. Epub 2013 May 14. — View Citation

Suprasert P, Srisomboon J, Charoenkwan K, Siriaungul S, Khunamornpong S, Siriaree S, Phongnarisorn C, Lorvidhaya V. Outcomes of abandoned radical hysterectomy in patients with stages IB-IIA cervical cancer found to have positive nodes during the operation. Int J Gynecol Cancer. 2005 May-Jun;15(3):498-502. doi: 10.1111/j.1525-1438.2005.15315.x. — View Citation

Tohyama A, Murakami M, Yoshino K. Strategies for the Treatment of Cervical Cancer with Bulky Pelvic Lymph Nodes: An Overview of the Current Evidence. J UOEH. 2020;42(4):317-325. doi: 10.7888/juoeh.42.317. — View Citation

Wang SC, Lin LC, Kuo YT, Lin YW. Radiographic Number of Positive Pelvic Lymph Nodes as a Prognostic Factor in Cervical Cancer Treated With Definitive Concurrent Chemoradiotherapy or Intensity-Modulated Radiotherapy. Front Oncol. 2018 Nov 30;8:546. doi: 10.3389/fonc.2018.00546. eCollection 2018. — View Citation

Yang J, Delara R, Magrina J, Magtibay P, Yi J, Langstraat C, Robertson M, Dinh T, Butler K. Comparing survival outcomes between surgical and radiographic lymph node assessment in locally advanced cervical cancer: A propensity score-matched analysis. Gynecol Oncol. 2020 Feb;156(2):320-327. doi: 10.1016/j.ygyno.2019.12.009. Epub 2019 Dec 14. — View Citation

Zhou J, Wu SG, Sun JY, Liao XL, Li FY, Lin HX, Yang LC, He ZY. Incorporation of the number of positive lymph nodes leads to better prognostic discrimination of node-positive early stage cervical cancer. Oncotarget. 2017 Apr 18;8(16):26057-26065. doi: 10.18632/oncotarget.15220. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	Progression-free survival	3 years
Secondary	OS	Overall survival	3 years
Secondary	Treatment-related complications	Treatment-related complications	3 years
Secondary	False positive rate & positive predictive value of bulky or multiple LN imaging	To determine the accuracy of LN metastasis in imaging study	6 months