AURORAX-0087A: GAG Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic ccRCC (AUR87A)

AURORAX-0087A: Glycosaminoglycan Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic Clear Cell Renal Cell Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Diagnostic test: GAG score

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 280

Contacts and Locations

• Study Contact: Name: Saeed Dabestani; Phone Number: +46(0)707198567; Email: saeed.dabestani@gmail.com

Study Locations

• Canada
  • Calgary, Canada
    • Recruiting
    • Prostate Cancer Centre
    • Contact: Bimal Bhindi
• Denmark
  • Aarhus, Denmark
    • Completed
    • Aarhus University Hospital
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital
    • Contact: Lars Lund
  • Roskilde, Denmark
    • Recruiting
    • Zealand University Hospital
    • Contact: Nessn Azawi
• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Central Hospital
    • Contact: Petrus Järvinen
    • Contact: Harry Nisen
• France
  • Créteil, France
    • Recruiting
    • Hôpital Henri Mondor
    • Contact: Alexandre Ingels
• Italy
  • Bologna, Italy
    • Recruiting
    • AOU San Orsola Malpighi
    • Contact: Lorenzo Bianchi
  • Florence, Italy
    • Recruiting
    • Careggi University Hospital
    • Contact: Riccardo Campi
    • Contact: Andrea Minervini
  • Milano, Italy
    • Recruiting
    • San Raffaele Hospital
    • Contact: Umberto Capitanio
  • Orbassano, Italy
    • Recruiting
    • Aou San Luigi Gonzaga
    • Contact: Francesco Porpiglia
  • Roma, Italy
    • Recruiting
    • Istituto Nazionale Tumori Regina Elena
    • Contact: Giuseppe Simone
  • Verona, Italy
    • Recruiting
    • AOU Integrata Verona
    • Contact: Alessandro Antonelli
• Portugal
  • Coimbra, Portugal
    • Recruiting
    • Hospital da Luz Coimbra
    • Contact: Lorenzo Marconi
• Spain
  • Gijón, Spain
    • Recruiting
    • Hospital Universitario Cabueñes
    • Contact: Sergio Fernandez-Pello
• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: John Åkerlund
• United Kingdom
  • Cambridge, United Kingdom
    • Recruiting
    • Addenbrooke's Hospital
    • Contact: Grant Stewart
  • Edinburgh, United Kingdom
    • Recruiting
    • Western General Hospital
    • Contact: Alexander Laird
  • Frimley, United Kingdom
    • Recruiting
    • Frimley Park Hospital
    • Contact: Neil Barber
  • London, United Kingdom
    • Recruiting
    • Royal Free Hospital
    • Contact: Alex Bex
  • London, United Kingdom
    • Recruiting
    • Guys & St Thomas Hospital
    • Contact: Rajesh Nair
  • Norwich, United Kingdom
    • Recruiting
    • Norfolk & Norwich University Hospital
    • Contact: Mark Rochester
  • Reading, United Kingdom
    • Recruiting
    • Royal Berkshire Hospital
    • Contact: Christopher Blick
  • Salford, United Kingdom
    • Recruiting
    • Salford Royal NHS Foundation Trust
    • Contact: Satish Maddineni
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University School of Medicine
      • Contact: Viraj Master
  • New York
    • New York, New York, United States, 10065
      • Completed
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Jose Karam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population is a representative sample of the North American and European population of ccRCC patients with LP ≥ 5 after curative intent surgery

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; 140 patients with a minimum follow-up of 12 months	Diagnostic test: GAG score; blood and urine samples to determine GAG scores
Cohort 2; up to 140 patients with a minimum follow-up of 12 months	Diagnostic test: GAG score; blood and urine samples to determine GAG scores

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Lead-time GAG vs. radiological recurrence among true positives	Lead-time GAG vs. radiological recurrence among true positives	minimum follow-up of 12 months

Collaborators and Investigators

• Sponsor: Elypta
• Investigators: Principal Investigator: Saeed Dabestani, Lund University, Dept. Clinical Sciences, Skåne University Hospital

Publications and helpful links

Helpful Links

• Official website for AURORAX-87A

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: July 1, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Recurrence
• Other Study ID Numbers: ECD-AUR87A001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Unidentified clinical and biochemical data will become available to the research community along with the publication of a scientific article related to the present investigation.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No