EORTC GUCG 2418 - STARBURST: Strategies for treatment adaptation following re-evaluation of the bladder after using primary neoadjuvant systemic therapies—An EORTC platform trial.

Abstract

TPS880 Background: The standard treatment for patient with muscle-invasive bladder cancer (MIBC) consists of neoadjuvant systemic therapy (NAT) followed by radical cystectomy (RC) or trimodal therapy (TMT). Currently, patients are not routinely reassessed after NAT and proceed directly to local treatment, leading to a missed opportunity for patients with complete or near complete response to benefit from bladder sparing strategies. On the other hand, for the non-responders, it is a missed opportunity to early systemic escalation. The platform will involve multiple steps. First, Starburst-1 (SB-1) will aim to create an effective multimodal signature that can predict effectively pathological complete response to NAT. Once the signature is validated, we will develop Starburst-2 (SB-2) as a platform in which we will test different risk-adapted strategies based on the response post NAT. Methods: In SB-1, we will enroll in a phase II, single arm, prospective cohort, patients with newly diagnosed MIBC (pT2-T4a N0-1 M0). All patients will be treated with standard of care (SOC) NAT followed by RC. All patients will be assessed before NAT by a cystoscopy, TURBT, urine cytology, bladder multiparametric MRI (mpMRI) using the NacVi-RADS score, blood and urine liquid biopsy. After completing the NAT, each patient will undergo a cystoscopy (+/- biopsy), SOC clinical and radiological workup (TAP CT +/- PET-FDG), a mpMRI and blood/urine collection. The primary endpoint of SB-1 is to prospectively evaluate the accuracy of the NacVI-RADS score to predict the pathological complete response defined as the absence of muscle invasive disease (ypT≥2 vs ypT0/a/1). Kappa score agreement between the MRI staging and RC pathological staging will also be addressed. Secondary endpoints include the assessment of new biomarkers including blood circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA), urine multiplex biomarkers, pathomics, radiomics and molecular alterations that could predict pathological response. In SB-2, de-escalation therapies and escalation therapies according to patients’ response to NAT will be tested in a prospective multi-arm cohort platform. NCT number: will be obtained before ASCO GU. Clinical trial information: Ongoing in clinical trials.gov.