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

February 17, 2025 updated by: John Taylor, University of Kansas Medical Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Not yet recruiting
        • Holden Comprehensive Cancer Center - The University of Iowa
        • Contact:
          • Michael O'Donnell, MD
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • The University of Kansas Cancer Center
        • Contact:
        • Contact:
          • John Taylor III, MD, MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intravenous ascorbic acid/vitamin C

2 Cycles Carboplatin Day 1 and Gemcitabine Days 1 and 8 (NAC)

+ Intravenous Vitamin C Days 1-28
Drug: Intravenous ascorbic acid/vitamin C
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post treatment pathological staging
Time Frame: Approximately 10 to 12 weeks
To assess pathologic downstaging rate in MIBC cisplatin-ineligible patients when IVC is added to a gemcitabine/carboplatin NAC regimen. Pre and Post treatment specimen pathology results evaluated per American Joint Committee on Cancer (AJCC) staging guidelines.
Approximately 10 to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess Quality of life (QOL)
Time Frame: Approximately 10 to 16 weeks
Overall change in participant-reported quality of life outcomes. Fact-Bladder (FACT-BI) Quality of life questionnaire as measurement tool.
Approximately 10 to 16 weeks
To measure Disease Free Survival (DFS)
Time Frame: Approximately 2 years
Disease free survival rate (DFS) among participants
Approximately 2 years
To measure Disease Specific Survival (DSS)
Time Frame: Approximately 2 years
Disease specific survival rate among participants
Approximately 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cellular outcome markers, IVC uptake, IVC specific mechanism markers, Cell death, Cell proliferation
Time Frame: During surgery
Tumor samples will be collected at timepoints as listed in the protocol study procedures and schedule of events table for evaluation of generally used cellular outcome markers, as well as markers for IVC specific mechanism, via the IRB approved BCa tumor bank (Taylor PI). Acetylated tubulin levels and transferrin receptor levels in tumor samples will be detected as IVC related markers. SLC23A2 (SVCT2, vitamin C tissue receptor) will be assessed for drug uptake. TUNEL staining will be used as a measure of cell death and Ki67 as a measure of cell proliferation. Circulating tumor DNA (ctDNA) will be assessed in serum as an additional marker of treatment efficacy and recurrence. In addition, single-cell sequencing will be used to define changes in specific tissue populations at TUR and RC to evaluate both biomarkers of response and potential mechanisms associated with IVC treatment. To monitor inflammation, urinary cytokines will be assessed via multiplex ELISA at RC (post-treatment).
During surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Kansas Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2025

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

June 26, 2024

First Submitted That Met QC Criteria

July 4, 2024

First Posted (Actual)

July 10, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 17, 2025

Last Verified

July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT-2024-IVC GC MIBC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bladder Cancer

Clinical Trials on Intravenous ascorbic acid/vitamin C

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belarus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe