Circulating Tumor Cell Reducing No-touch Nephrectomy (CITO-CERENE)

November 10, 2022 updated by: Tito Palmela Leitão, Hospital de Santa Maria, Portugal

No-touch Radical Nephrectomy Technique Reduces Circulating Tumor Cell Release in Renal Cell Carcinoma Patients - a Randomized Controlled Trial

This study will study circulating tumor cell (CTC) release during laparoscopic radical nephrectomy (LRN) for RCC. The main objective is to determine if CTC release can be reduced during RN by using a no-touch technique, with an early renal pedicle ligation. The investigators also aim to describe the CTC profile in terms of CTC count (CTCn), epithelial/mesenchymal status, and CTC cellular features in renal cell carcinoma (RCC) patients, stratified by "primary tumor, regional nodes, metastasis" (TNM) staging, histological subtype, and other clinical and radiological features.

Patients undergoing RN will enter a two-arm prospective single-center randomized controlled trial (RCT), comparing a no-touch RN technique, with direct pedicle ligation (Group A) vs. the more conventional approach of kidney traction and manipulation to reach the renal pedicle before its ligation (Group B).

A microfluidic size-based CTC isolation device will be used to capture and count CTCs from peripheral blood samples of these patients. CTCs will be identified by staining with antibodies to cytokeratin 8/18, vimentin, 4',6-diamidino-2-phenylindole (DAPI), and cluster of differentiation antigen 45 (CD45).

CTC release will be correlated with the disease-free survival (DFS), and overall survival (OS). The investigators will determine if CTC reducing no-touch radical nephrectomy technique improves these hard outcomes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will study CTC profile in RCC, and their release into the blood circulation during LRN.

Included patients will be referred to the Renal Cancer Unit of the North Lisbon University Hospital Center (CHLUN) Urology Department with the diagnosis of a renal mass eligible for a LRN. Patients will have their diagnosis confirmed, be appropriately staged, and their management options will be decided after a shared and informed decision process in light of the current European Association of Urology (EAU) Guidelines on RCC. Patients < 18 years old and pregnant women will be excluded. Patients will be adequately informed of the study protocol, and will sign a specific informed consent.

Patients undergoing LRN will enter a two-arm prospective single-center randomized controlled trial, comparing a no-touch technique, with direct pedicle ligation (Group A) vs. the conventional dissection, and ligation of the renal pedicle with kidney traction (Group B). A peripheral blood sample will be collected at arrival to the operating room. After that, Group A patients will undergo a no-touch RN, with the dissection being done through the Gerota's fascia plane until exposure of the corresponding great vessel (vena cava on the right side, and aorta on the left side) is obtained. The renal pedicle will be directly isolated, and ligated using Weck® clips with no kidney manipulation. Group B patients will undergo a more conventional approach, starting with opening of the Gerota's fascia, identification of the ureter, traction on the peri-renal fat below the ureter while dissecting cephalad until the renal pedicle is reached. The renal pedicle will then be isolated while maintaining traction on the kidney, and peri-renal fat, and ligated using Weck® clips. A second peripheral blood sample will be collected at the time of specimen extraction. A third and fourth peripheral blood samples will be collected at post-operative days 1 and 30, respectively, to study CTC post-op kinetics. All samples will collect 7.5 mL of peripheral blood.

Patients presenting with hypofunctioning kidneys with indication for total nephrectomy will be used as controls. Total nephrectomy patients will undergo the randomization protocol, in a control arm.

The CTCs will be isolated from peripheral blood samples using a microfluidics size-based CTC capture device - Ruby™. Whole blood samples will be injected into the devices at an 80 µL/min flow rate. The CTCs captured on the devices will then be stained with antibodies to 4',6-diamidino-2-phenylindole (DAPI) to identify cell nuclei, cluster of differentiation antigen 45 (CD45) to identify leukocytes, cytokeratin 8/18 to identify epithelial CTCs, and vimentin to identify mesenchymal CTCs or CTCs which have undergone epithelial-to-mesenchymal transition. Blood samples will be processed no more than 30 minutes after collection.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Portugal
    • Lisbon
      • Lisboa, Lisbon, Portugal, 1649-035
        • Urology Department - Hospital de Santa Maria

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Renal mass on renal imaging compatible with kidney cancer
  • Indication for laparoscopic radical nephrectomy

Exclusion Criteria:

  • History of other cancer (carcinoma)
  • Previous systemic therapy for renal cell carcinoma
  • human immunodeficiency virus (HIV) positive
  • Hepatitis C virus (HCV) positive
  • hepatitis B virus (HBV) positive

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: No-touch laparoscopic radical nephrectomy
Group A patients will undergo a no-touch laparoscopic radical nephrectomy, with the dissection being done through the Gerota's fascia plane until exposure of the corresponding great vessel (vena cava on the right side, and aorta on the left side) is obtained. The renal pedicle will be directly isolated, and ligated using Weck® clips with no kidney manipulation.
Procedure: No-touch laparoscopic radical nephrectomy
We aim to determine if a laparoscopic no-touch nephrectomy with an early renal pedicle ligation can decrease CTC release during surgery.
ACTIVE_COMPARATOR: Conventional laparoscopic radical nephrectomy
Group B patients will undergo a conventional laparoscopic radical nephrectomy approach, starting with opening of the Gerota's fascia, identification of the ureter, traction on the peri-renal fat below the ureter while dissecting cephalad until the renal pedicle is reached. The renal pedicle will then be isolated while maintaining traction on the kidney, and peri-renal fat, and ligated using Weck® clips.
Procedure: Conventional laparoscopic radical nephrectomy
Conventional laparoscopic radical nephrectomy, which implies manipulation of the kidney, opening of the Gerota's fascia, and manipulation of peri-nephric fat during dissection, and renal pedicle isolation.
OTHER: Laparoscopic total nephrectomy control arm
Control arm in which a laparoscopic total nephrectomy will be performed in patients with hypo-functioning kidneys, and no renal cell carcinoma.
Procedure: Laparoscopic total nephrectomy control arm
Control arm in which a laparoscopic total nephrectomy will be performed in non-cancer patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Circulating tumor cell count - intra-operative
Time Frame: Intra-operative
CTC count in peripheral blood after tumor specimen extraction
Intra-operative
Circulating tumor cell count - D1
Time Frame: Post-operative day 1
CTC count in peripheral blood at post-operative day 1
Post-operative day 1
Circulating tumor cell count - D30
Time Frame: Post-operative day 30
CTC count in peripheral blood at post-operative day 30
Post-operative day 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 3 year
Overall survival
3 year
Disease free survival
Time Frame: 3 year
Disease free survival
3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital de Santa Maria, Portugal

Collaborators

Centro Hospitalar Lisboa Norte
Instituto de Medicina Molecular João Lobo Antunes

Investigators

  • Principal Investigator: Tito P Leitão, MD, Faculdade de Medicina da Universidade de Lisboa

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 27, 2021

Primary Completion (ACTUAL)

May 18, 2022

Study Completion (ACTUAL)

May 18, 2022

Study Registration Dates

First Submitted

September 26, 2021

First Submitted That Met QC Criteria

September 26, 2021

First Posted (ACTUAL)

October 7, 2021

Study Record Updates

Last Update Posted (ACTUAL)

November 14, 2022

Last Update Submitted That Met QC Criteria

November 10, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0001 (Cancer Research Institute)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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