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AURORAX-087A: GAG Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic ccRCC (AUR87A)

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ClinicalTrials.gov Identifier: NCT04006405
Recruitment Status : Recruiting
First Posted : July 5, 2019
Last Update Posted : February 13, 2020
Sponsor:
Information provided by (Responsible Party):
Elypta

Brief 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.

Condition or disease Intervention/treatment
Clear Cell Renal Cell Carcinoma 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.

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Study Type : Observational
Estimated Enrollment : 280 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: AURORAX-087A: Glycosaminoglycan Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic Clear Cell Renal Cell Carcinoma
Actual Study Start Date : January 10, 2020
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : March 2022


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




Primary Outcome Measures :
  1. Sensitivity and specificity of GAG recurrence [ Time Frame: minimum follow-up of 12 months ]
    Sensitivity and specificity of GAG recurrence to LP≥5 ccRCC radiological or histologically verified recurrence with a minimum follow-up time of 12 months


Secondary Outcome Measures :
  1. Absolute and relative risk increase (ARI/RRI) of radiological recurrence [ Time Frame: within 6 months since last GAG score evaluation ]
    Absolute and relative risk increase (ARI/RRI) of radiological recurrence in patients with GAG recurrence versus no GAG recurrence

  2. Recurrence-free survival (RFS) [ Time Frame: minimum follow-up of 12 months ]
    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

  3. Positive and negative predictive value (PPV/NPV) of GAG recurrence [ Time Frame: minimum follow-up of 12 months ]
    Positive and negative predictive value (PPV/NPV) of GAG recurrence to LP ≥5 ccRCC radiological recurrence

  4. Area under the receiver-operating-characteristic curve (AUC) of GAG scores [ Time Frame: minimum follow-up of 12 months ]
    Area under the receiver-operating-characteristic curve (AUC) of GAG scores to LP ≥5 ccRCC radiological recurrence

  5. RFS, overall survival (OS) and cancer specific survival (CSS) [ Time Frame: follow-up time of 2 years and 5 years respectively after primary surgery ]
    RFS, overall survival (OS) and cancer specific survival (CSS) in patients with GAG recurrence versus no GAG recurrence

  6. Concordance-index (C-index) of preoperative GAG scores [ Time Frame: follow-up time of 2 years and 5 years respectively after primary surgery ]
    Concordance-index (C-index) of preoperative GAG scores versus risk nomograms for RFS and for CSS

  7. Lead-time GAG vs. radiological recurrence among true positives [ Time Frame: minimum follow-up of 12 months ]
    Lead-time GAG vs. radiological recurrence among true positives


Biospecimen Retention:   Samples With DNA
blood and urine samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
Criteria

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.

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): NCT04006405


Contacts
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Contact: Saeed Dabestani +46(0)707198567 saeed.dabestani@gmail.com

Locations
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United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Viraj Master         
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Ari Hakimi         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jose Karam         
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark
Contact: Tommy Nielsen         
Odense University Hospital Recruiting
Odense, Denmark
Contact: Lars Lund         
Zealand University Hospital Not yet recruiting
Roskilde, Denmark
Contact: Nessn Azawi         
Finland
Helsinki University Central Hospital Recruiting
Helsinki, Finland
Contact: Petrus Järvinen         
Contact: Harry Nisen         
Italy
Careggi University Hospital Not yet recruiting
Florence, Italy
Contact: Riccardo Campi         
Contact: Andrea Minervini         
San Raffaele Hospital Recruiting
Milano, Italy
Contact: Umberto Capitanio         
Portugal
Hospital da Luz Coimbra Not yet recruiting
Coimbra, Portugal
Contact: Lorenzo Marconi         
United Kingdom
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Contact: Grant Stewart         
Frimley Park Hospital Not yet recruiting
Frimley, United Kingdom
Contact: Neil Barber         
Guys & St Thomas Hospital Recruiting
London, United Kingdom
Contact: Rajesh Nair         
Royal Free Hospital Not yet recruiting
London, United Kingdom
Contact: Alex Bex         
Norfolk & Norwich University Hospital Recruiting
Norwich, United Kingdom
Contact: Mark Rochester         
Salford Royal NHS Foundation Trust Recruiting
Salford, United Kingdom
Contact: Satish Maddineni         
Sponsors and Collaborators
Elypta
Investigators
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Principal Investigator: Saeed Dabestani Lund University, Dept. Clinical Sciences, Skåne University Hospital

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Responsible Party: Elypta
ClinicalTrials.gov Identifier: NCT04006405    
Other Study ID Numbers: ECD-AUR87A001
First Posted: July 5, 2019    Key Record Dates
Last Update Posted: February 13, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Disease Attributes
Pathologic Processes