Intravenous (IV) Vitamin C With Chemotherapy for Cisplatin Ineligible Bladder Cancer Patients

Phase 1

Active, not recruiting

Brief Summary: Bladder cancer is a common disease with high rates of mortality, especially at advanced stages. Neo-adjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy is considered standard of care for patients with muscle invasive disease, as NAC improves surgical outcomes in these patients. However, some patients are ineligible for cisplatin-based chemotherapy due to other medical issues. Although a combination of carboplatin and gemcitabine has been used with limited success, most patients proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve both carboplatin and gemcitabine-based therapy in other models. This trial will add IVC to gemcitabine/carboplatin chemotherapy to evaluate whether co-treatment will increase therapeutic efficacy.

Recruitment & Eligibility

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) Performance Status = 0 -- 2
Cisplatin-ineligible, muscle invasive bladder cancer
Adequate organ and marrow functions
Women of child-bearing potential and men with partners of child-bearing potential must agree to use protocol specified forms of birth control

Exclusion Criteria

Patient simultaneously enrolled in any therapeutic clinical trial
Current or anticipated use of other investigational agents while participating in this study
Psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or breast feeding. 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
Prior systemic chemotherapy (prior intravesical therapy is allowed) and/ or prior radiation therapy to the urinary bladder
Uncontrolled intercurrent illness
Current consumption of tobacco products
History of glucose-6-phosphate dehydrogenase (G6PD) deficiency

Arm && Interventions

Group	Intervention	Description
IV Ascorbic Acid	Ascorbic Acid	IV Ascorbic Acid 25 grams (g) infused 2 times a week for 4 weeks

Primary Outcome Measures

Name	Time	Method
Post Treatment Pathological Staging	6 weeks after first IVC infusion at radical cystectomy	Post treatment specimen pathology results evaluated per the WHO TNM staging system. The staging system is a qualitative assessment based on the results of the physical exam, biopsy, imaging tests, and the results of surgery. The earliest stage cancers are called stage 0 (or carcinoma in situ), and then range from stages I (1) through IV (4). As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage IV, means a more advanced cancer.

Secondary Outcome Measures

Name	Time	Method
Disease Free Survival Rate (DFS) Among Participants	5 years	DFS will be defined as time from cystectomy to disease recurrence or death resulting from disease. DFS represents time from random assignment to cancer recurrence or death from any cause. Patients alive without disease progression at the time of analysis were censored at the date of last disease assessment.
Overall Change in Patient-reported Quality of Life Outcomes	Baseline, End of Treatment (completion of neoadjuvant therapy, Day 28), Post-surgery (6 weeks post-operative)	Scores evaluated per Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) version 4 - quality of life (QOL) questionnaire scores: * FACT-Bl total score range is 0-156, derived by the sum of the sub-scales. Higher scores indicate better QOL. * FACT-Bl includes five sub-scales: * Physical Well-being (PWB), score range of 0-28 * Social/Family Well-being (SWB), score range of 0-28 * Emotional Well-being (EWB), score range of 0-24 * Functional Well-being (FWB), score range of 0-28 * Bladder Cancer Subscale (BlCS), score range of 0-48 * Note: Negatively stated items are reversed by subtracting the response from "4".

Locations (3): The University of Kansas Cancer Center, Westwood Campus
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Kansas City, Kansas, United States
The University of Kansas Cancer Center (KUCC)
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Fairway, Kansas, United States
The University of Kansas Medical Center
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Kansas City, Kansas, United States