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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 : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
David Cibula, Charles University, Czech Republic

Brief Summary:

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

Detailed Description:

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):

  1. Patients with intra-operative detection of more advanced disease stage (> IB1)
  2. Patients with failure to detect SLN bilaterally (either no SLN detected or only on one side of the pelvis)
  3. 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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 600 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 7 Years
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 : November 2020
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Sentinel lymph node (SLN)
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
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



Primary Outcome Measures :
  1. 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 %).


Secondary Outcome Measures :
  1. Prevalence of symptomatic pelvic lymphocele [ Time Frame: 2 years ]
    Reduction in the prevalence of at least 30% to the reference prevalence (6%).

  2. Prevalence of lower extremity lymphedema [ Time Frame: 2 years ]
    Reduction in the prevalence of at least 30% to the reference prevalence (30%).

  3. 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)

  4. DFS (Disease-free survival) [ Time Frame: 2 years ]
    Disease-free survival after treatment with primary surgery until first recurrence.

  5. Pelvic DFS (Pelvic Disease-free survival) [ Time Frame: 2 years ]
    Disease-free survival after treatment with primary surgery until first recurrence within the pelvis.

  6. Quality of life (QoL) [ 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.

  7. Intra-operative morbidity [ Time Frame: 1 month ]
    Intra-operative morbidity will be evaluated using 5-grade "Dindo" Classification of surgical complications.

  8. 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

  9. DFS in SLN negative patients [ Time Frame: 2 years ]
    Disease free survival in patients with SLN negative on final ultrastaging

  10. 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.

  11. Overall survival [ Time Frame: 2 years ]
    Overall survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with early stages cervical cancer
Criteria

I) SLN study group:

Inclusion criteria:

A) Preoperative:

  1. FIGO stage IA1+LVSI; IA2; IB1
  2. No evidence of bulky or suspicious pelvic lymph nodes or distant metastases in preoperative conventional imaging studies
  3. Performance status ECOG: 0 - 1
  4. Age ≥ 18 years, ≤ 75 years
  5. Squamous cell carcinoma OR Adenocarcinoma usual type (HPV related)
  6. Suitable candidates for primary surgical treatment such as:

    • radical hysterectomy in tumors ≤ 4 cm in the largest diameter OR
    • fertility-sparing treatment in tumors ≤ 2 cm in the largest diameter
  7. History of second primary cancer only if > 5 years with no evidence of disease
  8. Approved and signed Informed consent

B) Intra-operative

  1. Bilateral SLN detection
  2. Negative intra-operative pathologic SLN evaluation (frozen section)
  3. No intra-operative evidence of more advanced disease (>IB1)

Exclusion Criteria:

  1. Neoadjuvant chemotherapy
  2. Pregnancy
  3. History of pelvic or abdominal radiotherapy
  4. HIV positivity / AIDS
  5. Adenosquamous cancer or adenocarcinoma unusual type (non HPV related - such as: mucinous, clear cell, mesonephric)

II) Control Group:

Inclusion criteria:

A) Preoperative:

  1. FIGO stage IA1 + LVSI; IA2; IB
  2. Performance status ECOG: 0-1
  3. Age ≥ 18 years, ≤ 75 years
  4. Patient is not pregnant
  5. No history of pelvic or abdominal radiotherapy
  6. Patient scheduled for surgical treatment including systematic pelvic lymphadenectomy
  7. Approved and signed Informed Consent

B) Intra-operative:

a) Systematic pelvic lymphadenectomy performed at least on one side of the pelvis

Exclusion criteria:

  1. Pregnancy
  2. History of pelvic or abdominal radiotherapy

Information from the National Library of Medicine

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


Contacts
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Contact: David Cibula, MD +420224967451 dc@davidcibula.cz
Contact: Ivana Nohova, PhD +420224967451 Ivana.Nohova@vfn.cz

Locations
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Czechia
Gynecologic Oncology Center in Prague Recruiting
Prague, Czechia, 15000
Contact: David Cibula, M.D.    +420603547055    dc@davidcibula.cz   
Contact: Ivana Nohova, PhD    +420224967451    Ivana.Nohova@vfn.cz   
Sponsors and Collaborators
Charles University, Czech Republic
Investigators
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Principal Investigator: David Cibula, MD Gynecologic Oncology Center, Department of Obstetrics and Gynecology, General University Hospital and 1st Faculty of Medicine, Charles University Prague, Czechia
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: David Cibula, MD, PhD, Professor, Charles University, Czech Republic
ClinicalTrials.gov Identifier: NCT02494063    
Other Study ID Numbers: CEEGOG CX-01
16-31643A ( Other Grant/Funding Number: Czech Research Council )
ENGOT-Cx 2 ( Other Identifier: ENGOT )
CEEGOG CX-01 ( Other Identifier: Central and Eastern European Gynecologic Oncology Group )
Protocol v2.0 (1st amendment) ( Other Identifier: SENTIX Steering Committee (22-May-2018) )
19-03-00023 ( Other Grant/Funding Number: Czech Research Council )
First Posted: July 10, 2015    Key Record Dates
Last Update Posted: August 4, 2020
Last Verified: August 2020
Keywords provided by David Cibula, Charles University, Czech Republic:
cervical cancer
sentinel lymph node
lymphadenectomy
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases