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Intravenous Vitamin C with Gemcitabine and Carboplatin for the Treatment of Patients with Bladder Cancer who Cannot Receive Cisplatin, A Forgotten Group Study

Trial Status: Active

This phase Ib / II trial studies the best dose and effect of vitamin C given together with gemcitabine and carboplatin in treating patients with bladder cancer who cannot receive cisplatin. Vitamin C is a nutrient that the body needs in small amounts to function and stay healthy. It helps fight infections, heal wounds, and keep tissues healthy. Chemotherapy drugs, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding IV vitamin C to gemcitabine and carboplatin may better help treat cancer. Vitamin C may help gemcitabine and carboplatin kill tumor cells.

Inclusion Criteria

  • Ability of participant OR legally authorized representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status = 0-2
  • Cisplatin-ineligible or declined muscle invasive bladder cancer. Cisplatin ineligibility will be defined based on Galsky criteria: * Common Terminology Criteria for Adverse Events (CTCAE) version (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
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9 g/dL
  • Creatinine clearance (estimated or calculated) >= 30 ml/min
  • Total bilirubin =< 2.0 mg/dl
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal
  • Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Normal glucose-6-phosphate dehydrogenase (G6PD) status
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use the forms of contraception listed below, prior to study entry, for the duration of study participation, and for WOMEN: 6 months after end of treatment (EOT), MEN: 3 months after EOT following completion of therapy. If a woman becomes pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) and is < 45 years of age * Men of child-bearing potential must not donate sperm while on this study and for 3 months after their last study treatment
  • Acceptable birth control methods include: * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: ** Oral ** Intravaginal ** Transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: ** Oral ** Injectable ** Implantable * Other methods: ** Intrauterine device (IUD) ** Intrauterine hormone-releasing system (IUS) ** Bilateral tubal occlusion ** Vasectomized partner ** Sexual abstinence, if this is the preferred and usual lifestyle of the participant

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 breastfeeding. There is a potential for congenital abnormalities and for this regimen to harm breastfeeding infants
  • Women of childbearing age expecting to conceive children while receiving study treatment and for 3 months after the last dose of study treatment
  • OTHER STUDY SPECIFIC CRITERIA
  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, or pure small cell carcinoma in the transurethral resection of bladder tumor (TURBT) sample
  • Prior systemic chemotherapy (prior intravesical therapy is allowed) for bladder cancer and/ or prior radiation therapy to the urinary bladder with curative intent for bladder cancer
  • 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
  • Current consumption of tobacco products, patients may be asked to quit for 2-3 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

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: John A Taylor
Phone: 913-588-2589

PRIMARY OBJECTIVE:

I. To assess pathologic downstaging rate in muscle invasive bladder cancer (MIBC) cisplatin-ineligible patients when intravenous ascorbic acid (vitamin C) (IVC) is added to a gemcitabine/carboplatin neoadjuvant chemotherapy (NAC) regimen.

SECONDARY OBJECTIVES:

I. To assess quality of life.

II. To measure disease free survival (DFS).

III. To measure disease specific survival (DSS).

EXPLORATORY OBJECTIVE:

I. Biomarkers for cell death, IVC related biomarkers and cellular outcome biomarkers will be evaluated in tumor samples at initial resection and radical cystectomy.

OUTLINE: This is a phase I, dose-escalation study of ascorbic acid, followed by a phase II study.

Patients receive ascorbic acid intravenously (IV) 2-3 times a week for 4 weeks in the absence of absence of disease progression or unacceptable toxicity. Patients also receive carboplatin IV on day 1 and gemcitabine IV on days 1 and 8. Patients then undergo standard of care radical cystectomy.

After completion of study treatment, patients are followed up at 30, 60, and 100 days, 3 and 6 months, 1, 3, and 5 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
University of Kansas Cancer Center

Principal Investigator
John A Taylor

  • Primary ID IIT-2019-IVC-CarboGem
  • Secondary IDs NCI-2020-11786
  • Clinicaltrials.gov ID NCT04046094