Grant to fund trial of intravenous ascorbate plus chemotherapy for MIBC

The US Department of Defense has awarded a $3.6 million grant to advance a phase 2 trial (NCT06493370) of high-dose intravenous ascorbate (vitamin C) plus chemotherapy (gemcitabine/carboplatin) in patients with muscle-invasive bladder cancer (MIBC), the University of Kansas Cancer Center announced in a news release.¹

The primary end point for the study is the rate of post-treatment pathological downstaging.

“Intravenous vitamin C achieves significantly higher levels in the blood than oral intake. Administering it intravenously allows us to reach supratherapeutic levels, where vitamin C can be toxic to cancer cells,” explained principal investigator John Taylor III, MD, MS, in the news release.¹ “[Additionally,] vitamin C is a comparatively low-cost and readily available therapy. For people who are ineligible for the standard chemotherapy regimen, this new approach has the potential to be practice changing.”

According to the news release, data from a phase 1 trial (NCT04046094) showed that the addition of intravenous ascorbate to chemotherapy led to tumor shrinkage in up to one-third of patients prior to cystectomy. Specifically, data presented at the 2022 American Urological Association Annual Meeting showed that the rate of downstaging in the study was greater than 36%.² Of those who achieved a pathological response, 75% achieved a complete response.

Regarding safety, there were few adverse events related to treatment, and patients were generally able to maintain their quality of life throughout treatment. In total, the study included 12 patients with MIBC.²

The phase 1 trial of the combination was conducted at the University of Kansas Cancer Center. The current phase 2 trial will include an additional site at the University of Iowa Holden Comprehensive Cancer Center in Iowa City.

“Researchers at the University of Iowa Holden Comprehensive Cancer Center are established experts on vitamin C, making them the perfect partner as we move into phase 2 of the trial,” Taylor added in the news release.¹ “This is a truly collaborative effort that is only possible at major academic medical centers like ours.”

In total, the open-label phase 2 trial plans to enroll 48 adult patients with MIBC who are ineligible or declined cisplatin-based neoadjuvant chemotherapy.³ To be eligible for enrollment, patients must have an ECOG performance score of 0 to 2, adequate organ function, and women of childbearing potential must have a negative serum pregnancy test 72 hours prior to initiating treatment.

According to the investigators, patients with MIBC who decline or are ineligible for cisplatin typically proceed straight to radical cystectomy within 12 weeks of their initial diagnosis. In this trial, patients will receive 2 cycles of chemotherapy with intravenous ascorbate before advancing to surgery. Specifically, intravenous ascorbate will be initially given as a dose escalation regimen starting at 25 g and titrated to up target peak plasma concentration. Ascorbate will then be given 2 times per week for the remaining cycles.

The primary end point for the study is the rate of post-treatment pathological downstaging. Secondary outcome measures are quality of life, disease-free survival, and disease-specific survival, as assessed for up to 2 years. The team also plans to assess cellular outcome markers, intravenous vitamin C uptake, intravenous vitamin C specific mechanism markers, cell death, and cell proliferation during surgery.

Patient recruitment for the phase 2 trial is expected to begin by the end of 2024, with primary completion of the study anticipated for December 2028.

References

1. New study aims to improve bladder cancer treatment with high-dose intravenous vitamin C. News release. University of Kansas Cancer Center. August 12, 2024. Accessed August 13, 2024. https://www.newswise.com/articles/new-study-aims-to-improve-bladder-cancer-treatment-with-high-dose-intravenous-vitamin-c

2. Taylor J, Parikh R, Chen Q, et al. Interim analysis NCT04046094: IV vitamin C with chemotherapy for cisplatin ineligible bladder cancer patients (CI-MIBC). Presented at: 2022 American Urological Association Annual Meeting; New Orleans, LA; May 13-16, 2022. Abstract LBA01-09. https://www.auajournals.org/doi/pdf/10.1097/JU.0000000000002669.09

3. Intravenous ascorbate plus gemcitabine/​carboplatin: A novel and cost-effective alternative with evident efficacy in patients with muscle invasive bladder cancer. ClinicalTrials.gov. Last updated July 10, 2024. Accessed August 13, 2024. https://clinicaltrials.gov/study/NCT06493370