LBA01-09: Interim analysis NCT04046094: IV Vitamin C With Chemotherapy for Cisplatin Ineligible Bladder Cancer Patients (CI-MIBC)

John Taylor, Rahul Parikh, Qi Chen, Benjamin Woolbright, Ping Chen, Elizabeth Wulff-Burchfield, Jeff Holzbeierlein, Jane Ledesma, Roy Jensen, Jeanne Drisko

Introduction: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ~40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting.  Patients usually proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve the efficacy of carboplatin and gemcitabine-based therapy in other models. This single-arm, Simon 2-stage, window of opportunity trial included IVC with single cycle GCa to evaluate pathologic downstaging.  We report on the interim first stage analysis of 12 patients.

Methods: Patients with newly diagnosed CI-MIBC were enrolled and received single cycle GCa and IVC titrated to peak plasma concentration of 350 to 400 mg/dL (~20 mM) for 21 days followed by cystectomy at 4-6 weeks from initiation of treatment. The primary outcome is pathological stage at cystectomy.  Patients are then followed per NCCN guidelines with standard of care bloodwork, physical exam and imaging studies until progression and/or death. QOL is being evaluated by Functional Assessment of Cancer Therapy-Bladder (FACT-Bl).

Results: All 12 patients completed GCa/IVC with 11 having had a cystectomy and 1 pending surgery.  Pathological downstaging (yp
Conclusions: Interim analysis of GCa-IVC NAC shows good tolerability with >36% rate of downstaging.  Of those with a pathological response, 75% achieved a CR.  Continuation criteria has been met for stage 2.  FACT-BI analysis and clinical follow up is ongoing and will be reported at study completion.

Source of Funding: NCATS/CTSA KU Frontiers: KU CTSI UL1TR002366, NCI Cancer Center Support Grant P30 CA168524