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

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

NCT ID: NCT06493370

Condition: Bladder Cancer

Conditions: Official terms:
Urinary Bladder Neoplasms
Ascorbic Acid

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: This phase 2 study is not randomized or blinded. All eligible participants will be enrolled to avoid bias and be evaluated for adverse events. Due to the small sample size, patients who do not complete neo-adjuvant therapy will be evaluated for toxicity but maybe replaced for efficacy analysis.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Intravenous ascorbic acid/vitamin C
Description: A dose escalation regimen will be initiated for each participant at a single dose of 25 g, titrated to up target peak plasma concentration. Once established, IVC will be administered intravenously 2 times per week for the remaining cycles
Arm group label: Intravenous ascorbic acid/vitamin C

Summary: This is a phase II, single arm, Simon two-stage design, trial, enrolling patients with cisplatin ineligible MIBC and/or those patients who decline cisplatin based NAC. Assess rates of pathologic downstaging and quality of life in MIBC cisplatin-ineligible/declined patients when IVC is added to gemcitabine-carboplatin NAC.

Detailed description: The investigator has hypothesized adding IVC to carbo/gem NAC will enhance pathological downstaging and improve QOL. The patients eligible for this study (cisplatin ineligible or declined with MIBC) typically proceed straight to cystectomy within 12 weeks of initial diagnosis. In this study, participants will receive two cycles of gemcitabine/carboplatin, along with IVC and then proceed to cystectomy.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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. Exclusion Criteria: - Simultaneously enrolled in any therapeutic clinical trial - Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study - Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements - Is pregnant or breastfeeding. There is a potential for congenital abnormalities and for this regimen to harm breast feeding infants - 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 - Has a severe known allergic reaction to any excipient contained in the study drug formulation - 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. - 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. - Histology of pure adenocarcinoma, pure squamous cell carcinoma, or pure small cell carcinoma in the TURBT sample - Current consumption of tobacco products, patients may be asked to quit for 2 weeks prior to enrollment - If tobacco use is suspected at any point during the trial, cotinine level will be obtained - History of G6PD deficiency - History of oxalate renal calculi - per discretion of treating physician

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Holden Comprehensive Cancer Center - The University of Iowa

Address:
City: Iowa City
Zip: 52242
Country: United States

Contact:
Last name: Michael O'Donnell, MD

Investigator:
Last name: Michael O'Donnell, MD
Email: Principal Investigator

Facility:
Name: The University of Kansas Cancer Center

Address:
City: Kansas City
Zip: 66160
Country: United States

Contact:
Last name: KUCC Navigation

Phone: 913-588-3671
Email: kucc_navigation@kumc.edu

Investigator:
Last name: John Taylor III, MD, MS
Email: Principal Investigator

Start date: December 1, 2024

Completion date: December 1, 2030

Lead sponsor:
Agency: University of Kansas Medical Center
Agency class: Other

Source: University of Kansas Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06493370
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