Intravenous Ascorbate Plus Gemcitabine/Carboplatin: A Novel and Cost-Effective Alternative With Evident Efficacy in Patients With Muscle Invasive Bladder Cancer

Prior treatment

• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Women of childbearing age expecting to conceive children while receiving study treatment and for 6 months after the last dose of study treatment. Men expecting to conceive children while receiving study treatment and for 3 months after the last dose of study treatment
• Active Grade 3 or 4 (per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0109) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.
• Current consumption of tobacco products, patients may be asked to quit for 2 weeks prior to enrollment

Other illness

• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Has a severe known allergic reaction to any excipient contained in the study drug formulation
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, as determined per treating physician.
• History of G6PD deficiency
• History of oxalate renal calculi - per discretion of treating physician

Other

• Simultaneously enrolled in any therapeutic clinical trial
• Is pregnant or breastfeeding. There is a potential for congenital abnormalities and for this regimen to harm breast feeding infants
• Histology of pure adenocarcinoma, pure squamous cell carcinoma, or pure small cell carcinoma in the TURBT sample
• If tobacco use is suspected at any point during the trial, cotinine level will be obtained

• Ability of participant to understand this study, and participant willingness to sign a written informed consent
• Consent to participate in biorepository protocol number GUB-BCR-001, KU IRB Approved HSC # STUDY00141546
• Males and females age ≥ 18 years
• ECOG Performance Status (PS) 0 - 2
• Women of childbearing potential must have a negative serum pregnancy test 72 hours prior to initiating treatment.
• Diagnosis/disease status Cisplatin-ineligible or declined muscle invasive bladder cancer. Cisplatin ineligibility will be defined based on Galsky criteria: CTCAE ver. 5.0 Grade 2 or greater peripheral neuropathy; CTCAE ver. 5.0 Grade 2 or greater hearing loss; Creatinine clearance estimated or calculated \< 60 ml/min; NYHA class II or greater congestive heart failure
• Adequate organ function, defined as follows: Absolute Neutrophil Count \>1.5K/UL. (NOTE: Patients with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 based on discretion of the treating physician.); Platelets \>100K/UL; Hemoglobin ≥ 9 g/dL; Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation; Total bilirubin ≤ 2.0 x ULN; Aspartate aminotransferase (AST \[SGOT\]) and alanine aminotransferase (ALT \[SGPT\]) ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN; Normal Glucose-6-phosphate dehydrogenase (G6PD) status
• Women of child-bearing potential (WOCBP) and men with partners of child-bearing potential must agree not to donate sperm (men), to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for WOMEN: 6 months after EOT, MEN: 3 months after EOT following completion of therapy.