Clinical trial NCT06493370: Intravenous Ascorbate Plus Gemcitabine/Carboplatin: A Novel and Cost-Effective Alternative With Evident Efficacy in Patients With Muscle Invasive Bladder Cancer
Official title: Intravenous Ascorbate Plus Gemcitabine/Carboplatin: A Novel and Cost-Effective Alternative With Evident Efficacy in Patients With Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bladder Cancer
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2024-07-10
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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

Brief 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.

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

Primary outcomes:
measure: Post treatment pathological staging
timeFrame: Approximately 10 to 12 weeks
Secondary outcomes:
measure: To assess Quality of life (QOL)
timeFrame: Approximately 10 to 16 weeks
measure: To measure Disease Free Survival (DFS)
timeFrame: Approximately 2 years
measure: To measure Disease Specific Survival (DSS)
timeFrame: Approximately 2 years
Other outcomes:
measure: Cellular outcome markers, IVC uptake, IVC specific mechanism markers, Cell death, Cell proliferation
timeFrame: During surgery
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center - The University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
Study officials:
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