Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04006405
Other study ID # ECD-AUR87A001
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date January 10, 2020
Est. completion date February 2025

Study information

Verified date May 2023
Source Elypta
Contact Saeed Dabestani
Phone +46(0)707198567
Email saeed.dabestani@gmail.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

AUR87A is an observational prospective multicenter diagnostics test cohort study for detection of renal cell carcinoma recurrence as determined by the reference standard, which is imaging using computed tomography (CT) of the chest and abdomen at defined intervals after primary surgery.


Description:

Non-metastatic clear cell renal cell carcinoma (ccRCC) recur in ~20% of cases within 5 years after radical surgery. Current postoperative follow-up protocols, being schematic and at best based on risk of recurrence scores, are sub-optimal for early detection of recurrences which could potentially be available for curative management. Blood and urine collected glycosaminoglycans (GAGs) are promising novel class of biomarkers from which a new diagnostic test based on so called GAG scores has been developed. GAG scores have accurately distinguished localized/locally-advanced and advanced RCC from healthy subjects. AUR87A features an adaptive design. The primary endpoint analysis is conducted when 30 events (i.e. recurrences) are reached - expected at 140 patients with a minimum follow-up of 12 months (cohort 1). An interim analysis at 15 events is conducted to verify whether the sensitivity and specificity estimates are in line with the study assumptions. In case of futility, the GAG scores formulations and/or cut-offs are optimized based on data from cohort 1. The primary endpoints are then validated on a second independent cohort, powered depending on the results from cohort 1. This second cohort is estimated in 140 patients (cohort 2). In case of non-futility, cohort 2 may be used as external validation. AUR87A will prospectively enroll an estimated 280 non-metastatic ccRCC patients curatively treated with surgery (partial or radical nephrectomy). Patients are followed-up longitudinally using GAG scores in blood and urine every 3 months after surgery, alongside the current standard follow-up protocol, i.e. imaging, as reference standard. The hypothesis of AUR87A is that postoperative increase of the GAG scores, so called "GAG recurrence ", can predict or detect recurrence at an earlier time-point compared to the reference standard, referred to as "radiological recurrence", and thereby improve the clinical utility of current follow-up protocols.


Recruitment information / eligibility

Status Recruiting
Enrollment 280
Est. completion date February 2025
Est. primary completion date January 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: Pre-screening inclusion criteria - Size of primary tumor >4cm (>cT1a) in greatest dimension on pre-operative abdominal CT-scan - Size of primary tumor =4cm is allowed if pre-operative abdominal CT-scan shows suspected RCCs with radiological sign of venous tumor thrombus (renal vein or caval). - Pre-operative CT-scan of chest and abdomen show no signs of metastatic disease - Localized and biopsy proven clear cell RCC (ccRCC) under active surveillance which at timepoint of study recruitment, opted for surgery because of growth rate of primary tumor to a size > 4cm - Elected for curative intent surgery for RCC Final screening inclusion criteria - Any gender being 18 years or older at timepoint of final inclusion - In postoperative pathology report shown to be ccRCC subtype according to 8th Edition of the American Joint Committee on Cancer (AJCC) - Leibovich points (LP) =5 according to Leibovich score system (2003) - If pathology report shows multiple subtypes in same tumor, as long as the majority of tumor is ccRCC (>50%), participant can be included Exclusion Criteria: Pre-screening exclusion criteria - TNM-stage T(any) N(any) M1 according to AJCC, i.e. metastatic disease at diagnosis - Absence of preoperative chest imaging (chest CT) within 60 days prior to primary surgery - Previous history of curatively treated for other cancers, still not deemed fully cured and participant still under surveillance for said cancer - Participants offered active surveillance for RCC instead of curative intent surgery - Participants offered any type of thermal ablation treatment instead of surgery, i.e. LP cannot be assessed Final screening exclusion criteria - Participants with AJCC cN0 status at preoperative imaging in whom a clinically suspicious regional lymph-node metastases (enlarged lymph node(s)) is noted during primary surgery, but who subsequently do not undergo any lymph node dissection. (Note: participants with cN0 status at pre-operative imaging and no clinical signs of regional lymph node metastases during primary surgery can still be included irrespective of lymph node dissection having been performed, i.e. being pN0 or pN1 if it is performed or pNx if it is not performed) - Participants with AJCC cN1 status at pre-operative imaging in which lymph node dissection is not performed (i.e. pNx). - Elected for any adjuvant therapy (i.e. systemic therapy) outside or within any clinical study - Non-clear cell RCC histology or benign tumor (i.e. oncocytoma and angiomyolipoma, which are the most common benign types, but also any other rare types of benign renal tumors) after pathological analysis - Any hereditary form of RCC (e.g. Von Hippel-Lindau, Birt-Hogg-Dubé, Hereditary Papillary RCC) - RCC with pure sarcomatoid differentiation, also called sarcoma of the kidney - Previous history of curatively treated for RCC with a suspected de novo RCC in the remaining kidney tissue - Prior or current use of instillation therapy with hyaluronic acid and/or chondroitin sulfate (HA-CS). - Use of heparin, including low molecular weight heparin (e.g. Enoxaparin, Dalteparin, Tinzaparin) for concurrent disease in need of blood dilution (e.g. ongoing deep vein thrombosis or lung emboli). Note: use of of heparin for thrombus prophylaxis in conjunction with primary surgery or postoperatively =4 weeks will be allowed. - Patients who were not radically operated during primary surgery with the exception of histological positive surgical margin in participants who have undergone partial nephrectomy.

Study Design


Intervention

Diagnostic Test:
GAG score
blood and urine samples to determine GAG scores

Locations

Country Name City State
Canada Prostate Cancer Centre Calgary
Denmark Aarhus University Hospital Aarhus
Denmark Odense University Hospital Odense
Denmark Zealand University Hospital Roskilde
Finland Helsinki University Central Hospital Helsinki
France Hôpital Henri Mondor Créteil
Italy AOU San Orsola Malpighi Bologna
Italy Careggi University Hospital Florence
Italy San Raffaele Hospital Milano
Italy AOU San Luigi Gonzaga Orbassano
Italy Istituto Nazionale Tumori Regina Elena Roma
Italy AOU Integrata Verona Verona
Portugal Hospital da Luz Coimbra Coimbra
Spain Hospital Universitario Cabueñes Gijón
Sweden Sahlgrenska University Hospital Gothenburg
United Kingdom Addenbrooke's Hospital Cambridge
United Kingdom Western General Hospital Edinburgh
United Kingdom Frimley Park Hospital Frimley
United Kingdom Guys & St Thomas Hospital London
United Kingdom Royal Free Hospital London
United Kingdom Norfolk & Norwich University Hospital Norwich
United Kingdom Royal Berkshire Hospital Reading
United Kingdom Salford Royal NHS Foundation Trust Salford
United States Emory University School of Medicine Atlanta Georgia
United States MD Anderson Cancer Center Houston Texas
United States Memorial Sloan Kettering Cancer Center New York New York

Sponsors (1)

Lead Sponsor Collaborator
Elypta

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Finland,  France,  Italy,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Sensitivity and specificity of GAG recurrence Sensitivity and specificity of GAG recurrence to LP=5 ccRCC radiological or histologically verified recurrence with a minimum follow-up time of 12 months minimum follow-up of 12 months
Secondary Absolute and relative risk increase (ARI/RRI) of radiological recurrence Absolute and relative risk increase (ARI/RRI) of radiological recurrence in patients with GAG recurrence versus no GAG recurrence within 6 months since last GAG score evaluation
Secondary Recurrence-free survival (RFS) Recurrence-free survival (RFS) in the LP=5 ccRCC for GAG recurrence vs. no GAG recurrence with a minimum follow-up time of 12 months minimum follow-up of 12 months
Secondary Positive and negative predictive value (PPV/NPV) of GAG recurrence Positive and negative predictive value (PPV/NPV) of GAG recurrence to LP =5 ccRCC radiological recurrence minimum follow-up of 12 months
Secondary Area under the receiver-operating-characteristic curve (AUC) of GAG scores Area under the receiver-operating-characteristic curve (AUC) of GAG scores to LP =5 ccRCC radiological recurrence minimum follow-up of 12 months
Secondary RFS, overall survival (OS) and cancer specific survival (CSS) RFS, overall survival (OS) and cancer specific survival (CSS) in patients with GAG recurrence versus no GAG recurrence follow-up time of 2 years and 5 years respectively after primary surgery
Secondary Concordance-index (C-index) of preoperative GAG scores Concordance-index (C-index) of preoperative GAG scores versus risk nomograms for RFS and for CSS follow-up time of 2 years and 5 years respectively after primary surgery
Secondary Lead-time GAG vs. radiological recurrence among true positives Lead-time GAG vs. radiological recurrence among true positives minimum follow-up of 12 months
See also
  Status Clinical Trial Phase
Completed NCT03163667 - CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC) Phase 2
Terminated NCT02628535 - Safety Study of MGD009 in B7-H3-expressing Tumors Phase 1
Withdrawn NCT02307474 - A Pilot Study of SBRT With Adjuvant Pazopanib for Renal Cell Cancer N/A
Completed NCT00101114 - Sorafenib and Interferon Alfa in Treating Patients With Metastatic or Unresectable Kidney Cancer Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Recruiting NCT05363631 - Seleno-L Methionine (SLM)-Axitinib-Pembrolizumab Phase 1/Phase 2
Terminated NCT01198158 - Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy Phase 3
Completed NCT00378703 - Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer Phase 2
Recruiting NCT06138496 - Cadonilimab Combination With Lenvatinib as Neoadjuvant Therapy for ccRCC Phase 2
Recruiting NCT06088134 - Contrast-enhanced CT-based Deep Learning Model for Preoperative Prediction of Disease-free Survival (DFS) in Localized Clear Cell Renal Cell Carcinoma (ccRCC)
Recruiting NCT06049576 - Nivolumab and Ipilimumab With and Without Camu Camu for the Treatment of Patients With Metastatic Renal Cell Carcinoma Phase 1
Active, not recruiting NCT01038778 - Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer Phase 1/Phase 2
Recruiting NCT05536141 - A Phase 1 Study of AB521 Monotherapy and Combination Therapies in Renal Cell Carcinoma and Other Solid Tumors Phase 1
Recruiting NCT05119335 - A Study of NKT2152, a HIF2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1/Phase 2
Completed NCT01243359 - Sunitinib Malate and Bevacizumab in Treating Patients With Kidney Cancer or Advanced Solid Malignancies Phase 1
Terminated NCT00098618 - Sorafenib and Interferon Alfa in Treating Patients With Locally Advanced or Metastatic Kidney Cancer Phase 2
Recruiting NCT05620134 - Study of JK08 in Patients With Unresectable Locally Advanced or Metastatic Cancer Phase 1/Phase 2
Recruiting NCT06052852 - Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies Phase 1/Phase 2
Completed NCT03680521 - Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma Phase 2
Recruiting NCT06195150 - Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer