Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date July 1, 2019
First Posted Date July 5, 2019
Last Update Posted Date February 13, 2020
Actual Study Start Date January 10, 2020
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 2, 2019)
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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 2, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title AURORAX-087A: GAG Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic ccRCC
Official Title AURORAX-087A: Glycosaminoglycan Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic Clear Cell Renal Cell Carcinoma
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
blood and urine samples
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
Condition Clear Cell Renal Cell Carcinoma
Intervention Diagnostic Test: GAG score
blood and urine samples to determine GAG scores
Study Groups/Cohorts
  • Cohort 1
    140 patients with a minimum follow-up of 12 months
    Intervention: Diagnostic Test: GAG score
  • Cohort 2
    up to 140 patients with a minimum follow-up of 12 months
    Intervention: Diagnostic Test: GAG score
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 2, 2019)
280
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Saeed Dabestani +46(0)707198567 saeed.dabestani@gmail.com
Listed Location Countries Denmark,   Finland,   Italy,   Portugal,   United Kingdom,   United States
Removed Location Countries Norway
 
Administrative Information
NCT Number NCT04006405
Other Study ID Numbers ECD-AUR87A001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
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.
Responsible Party Elypta
Study Sponsor Elypta
Collaborators Not Provided
Investigators
Principal Investigator: Saeed Dabestani Lund University, Dept. Clinical Sciences, Skåne University Hospital
PRS Account Elypta
Verification Date February 2020