Sentinel Lymph Node Biopsy in Patients With Early Stages Cervical Cancer (SENTIX)
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|ClinicalTrials.gov Identifier: NCT02494063|
Recruitment Status : Recruiting
First Posted : July 10, 2015
Last Update Posted : December 17, 2018
To evaluate whether a less radical surgical approach with sentinel lymph node biopsy is non-inferior to treatment with systematic pelvic lymphadenectomy.
The null hypothesis is that the recurrence rate after SLN biopsy is non-inferior to the reference recurrence rate of 7 % (at the 24th month of follow-up) in patients after systematic pelvic lymphadenectomy, but that the less radical surgery is associated with significantly lower postoperative morbidity.
|Condition or disease||Intervention/treatment|
|Cervical Cancer||Procedure: Sentinel lymph node biopsy Procedure: At least unilateral systematic pelvic lymph node dissection|
Patients will be enrolled in the study at the time of surgery planning; at this point, a patient´s consent will be requested if inclusion criteria are fulfilled (histological type, FIGO stage, age, performance status, lymph node clinical status). The following procedures will be provided prior to surgery: clinical staging (MRI or EUS), medical data collection, adverse events assessment, lymphedema assessment, quality of life questionnaire, ECOG performance status, weight and height, standard pre-operative laboratory workup, pregnancy test if clinically indicated.
Surgery should be done within 6 weeks of the imaging study (MRI or expert US). During the surgery, local or distant cancer spread outside of the cervix will be excluded, SLN will be detected, and all SLN will be sent for intra-operative pathologic evaluation. In patients with SLN detection on both sides of the pelvis no other lymph nodes will be removed and they will continue in the study. SLN biopsy will be followed by radical hysterectomy (type B, C1, or C2) or fertility-sparing procedure, according to the pre-operative plan.
Intra-operatively, three groups of patient will be excluded from the SLN study group (though they can be included in the control group):
- Patients with intra-operative detection of more advanced disease stage (> IB1)
- Patients with failure to detect SLN bilaterally (either no SLN detected or only on one side of the pelvis)
- Patients with intra-operative pathologic detection of macrometastases or micrometastases in SLN
In these patients who were excluded from the study group, further surgery and adjuvant treatment will be provided according to the institutional guidelines. These patients will remain in a database and reasons for their exclusion from the SLN study group will be entered into the SIS (Form 2).
A control group will be established to compare postoperative morbidity in patients after SLN biopsy only and after complete pelvic lymphadenectomy. Patients in whom complete lymphadenectomy was performed at least on one side of the pelvis will be eligible for the control group.
In patients, who continue in the study, all SLNs will be processed by pathologists according to the protocol for SLN ultrastaging (Chapter 7.4.2; Appendix 11). If macrometastases or micrometastases or isolated tumor cells are detected in any of the SLNs by pathologic ultrastaging after the surgery, adjuvant radiotherapy will be recommended to the patient. No adjuvant treatment will be offered to those with negative final lymph node status, confirmed pre-operative disease FIGO stage (IA1 - IB1), and adequately performed radical hysterectomy with negative parametrial and vaginal margins.
Follow-up will consist of visits at regular intervals of 6 months after the surgery (additional visits in shorter intervals can be scheduled according to institutional guidelines). The following procedures will be provided at each visit during the follow-up period: pelvic examination, symptomatic lymphocele assessment, quality of life assessment (6 and 12 months after the surgery), adverse events assessment, and secondary lower extremity lymphedema assessment (2 years after surgery). Other imaging studies will be done only if clinically indicated. Any postoperative complication or disease recurrence will be managed according to the institutional guidelines.
|Study Type :||Observational|
|Estimated Enrollment :||600 participants|
|Official Title:||A Prospective Observational Trial on Sentinel Lymph Node Biopsy in Patients With Early Stage Cervical Cancer|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2021|
Only sentinel lymph node biopsy, no further pelvic lymph nodes removal, radical hysterectomy.
Procedure: Sentinel lymph node biopsy
Bilateral sentinel lymph node biopsy, pathologic ultrastaging
Control group is composed by either those who were enrolled into the trial, but who did not fulfil intra-operative criteria (especially failure to detect SLN on both pelvic side walls) or those in whom systematic lymphadenectomy is planned upfront.
Procedure: At least unilateral systematic pelvic lymph node dissection
- Recurrence rate at the 24th month of follow-up (cervical recurrences after fertility-sparing procedures will be excluded) [ Time Frame: 24 months ]Recurrence rate (RR) will be estimated at the 24th month of follow-up to prove a non-inferiority of SLN biopsy to the reference value (RR 24th month: 7 %).
- Prevalence of symptomatic pelvic lymphocele [ Time Frame: 2 years ]Reduction in the prevalence of at least 30% to the reference prevalence (6%).
- Prevalence of lower extremity lymphedema [ Time Frame: 2 years ]Reduction in the prevalence of at least 30% to the reference prevalence (30%).
- Postoperative morbidity [ Time Frame: 2 years ]Early postoperative morbidity (30 days after surgery) will be evaluated using 5-grade "Dindo" Classification of surgical complications. Late postoperative morbidity (from 30 days up to 2 years after surgery) will be evaluated using Common Terminology Criteria for Adverse Events v4.0 (CTCAE)
- DFS (Disease Free survival) [ Time Frame: 2 years ]
- Pelvic DFS (Pelvic Disease Free Survival) [ Time Frame: 2 years ]
- Quality of life [ Time Frame: 1 year ]The quality of life (QoL) will be assessed by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 self-administered multi-dimensional scale cancer specific questionnaire, which is validated in 81 languages. It consists of 5 function scales, three symptom scales, six single-items and a global QoL score.
- Intra-operative morbidity [ Time Frame: 1 month ]Intra-operative morbidity will be evaluated using 5-grade "Dindo" Classification of surgical complications.
- FNR (False Negative Rate) of intra-operative pathologic SLN evaluation [ Time Frame: 2 years ]Proportion of patients with lymph nodes negative on intraoperative evaluation but positive on final ultrastaging
- DFS in SLN negative patients [ Time Frame: 2 years ]Disease free survival in patients with SLN negative on final ultrastaging
- Recurrence rate safety margins [ Time Frame: 2 years ]Recurrence rate safety margin (> 0.12) as the study stopping rule will be examined when the first 30, 60,150 and 300 patients complete the 12-month follow-up.
- Overall survival [ Time Frame: 2 years ]Overall survival
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02494063
|Contact: David Cibula, MDfirstname.lastname@example.org|
|Contact: Ivana Nohova, PhD||+420224967451||Ivana.Nohova@vfn.cz|
|Principal Investigator:||David Cibula, MD||Gynecologic Oncology Center, Department of Obstetrics and Gynecology, General University Hospital in Prague and 1st Medical Faculty of the Charles University, Prague, Czech Republic|