Clear Cell Renal Cell Carcinoma
Conditions
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.
Interventions
DIAGNOSTIC_TESTGAG score
blood and urine samples to determine GAG scores
Sponsors
Elypta
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and specificity of GAG recurrence | 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
| Measure | Time frame | Description |
|---|---|---|
| Absolute and relative risk increase (ARI/RRI) of radiological recurrence | 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) | 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 | 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 | 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) | 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 | 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 | minimum follow-up of 12 months | Lead-time GAG vs. radiological recurrence among true positives |
Countries
Belgium, Canada, Denmark, Finland, France, Italy, Portugal, Spain, Sweden, United Kingdom, United States
Outcome results
None listed