Botensilimab + Balstilimab and Diet + Vitamin C for Colorectal Cancer

Recruiting at 1 trial location

Overseen By Charlean Ketchens, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Must not be taking: Diabetes medications, Oral vitamin C

Disqualifiers: Diabetes, Autoimmune disease, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 31

Duration: Up to 2 years

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial tests the safety, side effects, and effectiveness of botensilimab, and balstilimab in combination with a fasting mimicking diet and high dose vitamin C in treating patients with KRAS-mutant metastatic colorectal cancer. Botensilimab and balstilimab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. KRAS is protein found on some tumor cells that is involved in the growth of tumor cells. KRAS mutant cells have been found to be more sensitive to vitamin C induced growth suppression in the presence of low-sugar (glucose). A fasting mimicking diet, a plant-based, calorie reduced, low-sugar diet alternating with refeeding periods, may positively change the way the body responds to cancer treatment. Vitamin C is a nutrient that the body needs in small amounts to function and stay healthy. It is an antioxidant that that can help prevent cell damage and may block growth and spread of tumor cells. Botensilimab and balstilimab in combination with a fasting mimicking diet and high dose vitamin C may be safe, tolerable and effective in treating patients with KRAS-mutant metastatic colorectal cancer.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any medications that cannot be safely stopped during fasting periods or that cannot be safely taken without food. If you are on such medications, you may not be eligible to participate.

What data supports the effectiveness of the drug Botensilimab + Balstilimab and Diet + Vitamin C for colorectal cancer?

Research suggests that high-dose vitamin C, when combined with standard chemotherapy regimens like FOLFOX, may enhance treatment effectiveness in metastatic colorectal cancer. Additionally, new chemotherapeutic agents and targeted therapies have shown promise in improving survival rates for advanced colorectal cancer. ^{1 2 3 4 5}

What makes the Botensilimab + Balstilimab and Diet + Vitamin C treatment unique for colorectal cancer?

This treatment is unique because it combines Botensilimab and Balstilimab, which are immune checkpoint inhibitors that help the immune system attack cancer cells, with a high-dose Vitamin C regimen. High-dose Vitamin C has been shown to selectively kill certain colon cancer cells, potentially enhancing the effectiveness of the immune therapy. ^{1 5 6 7 8}

Research Team

Diana Hanna, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for patients with metastatic colorectal cancer that has a specific mutation called KRAS. Participants should be interested in combining standard cancer treatments with dietary changes and vitamin supplements.

Inclusion Criteria

I am 18 years old or older.

I don't have any other cancers that need treatment right now.

Platelets ≥ 75,000/mcL

Exclusion Criteria

I don't expect to need any other cancer treatments during the trial.

I don't have any severe side effects from previous treatments, except for possible nerve issues or hair loss.

I have had a transplant of tissue or an organ from another person, except for a cornea transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive botensilimab, balstilimab, and vitamin C intravenously, along with a fasting mimicking diet, in 42-day cycles for up to 2 years

Up to 2 years

Visits on days 1, 15, and 29 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

6 months

Follow-up at 30 days and every 3 months

Treatment Details

Interventions

• Balstilimab
• Botensilimab
• Dietary Intervention
• Vitamin C

Trial Overview The trial is testing the combination of two monoclonal antibodies, Botensilimab and Balstilimab, alongside a special low-sugar diet designed to mimic fasting and high doses of Vitamin C. The goal is to see if this combo can help stop the growth and spread of cancer cells more effectively.

Participant Groups

Group I: Treatment (botensilimab, balstilimab, FMD, vitamin C) Experimental Treatment 7 Interventions

Patients receive botensilimab IV over 30 minutes on day 1 of each cycle for up to 4 cycles. Patients receive balstilimab IV over 30 minutes and vitamin C IV over 30 minutes on days 1, 15 and 29 of each cycle. Patients undergo a FMD on days -4 to -1 of each cycle. Cycles repeat every 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT scans and MRI throughout the study.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 442 patients with metastatic colorectal cancer, adding high-dose vitamin C to standard chemotherapy (FOLFOX ± bevacizumab) did not improve progression-free survival compared to chemotherapy alone, with median PFS of 8.6 months versus 8.3 months.

However, patients with RAS mutations showed a significant benefit from the addition of vitamin C, achieving a longer median PFS of 9.2 months compared to 7.8 months with chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study). Wang, F., He, MM., Xiao, J., et al.[2023]

Recent advancements in systemic therapy for advanced colorectal cancer, including new chemotherapeutic agents like irinotecan, oxaliplatin, and capecitabine, have extended median survival for patients by up to 21 months.

The emergence of targeted therapies is promising, suggesting that some patients with advanced colorectal cancer may achieve long-term survival even without surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in previously untreated advanced colorectal cancer. Penland, SK., Goldberg, RM.[2018]

Recent advancements in the treatment of colorectal cancer, including the use of oxaliplatin and irinotecan alongside fluorouracil, have significantly improved patient outcomes, with over 75% of patients with localized disease remaining recurrence-free at 3 years.

Targeted therapies that focus on the vascular endothelial growth factor and epidermal growth factor pathways are now essential in treating colorectal cancer, contributing to a survival rate of up to 50% for patients with advanced unresectable disease at 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer. Gill, S., Blackstock, AW., Goldberg, RM.[2023]

Fruquintinib, a VEGFR inhibitor, significantly improved progression-free survival (PFS) by 3.7 months in metastatic colorectal cancer patients compared to placebo, demonstrating its efficacy in treatment-refractory cases.

The safety profile of fruquintinib was consistent with other VEGFR tyrosine kinase inhibitors, with common severe side effects including hypertension and hand-foot skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. Xu, RH., Li, J., Bai, Y., et al.[2022]

In a phase 1 study involving 36 patients with metastatic colorectal or gastric cancer, the maximum tolerated dose of ascorbic acid (AA) was not reached, establishing a recommended phase 2 dose of 1.5 g/kg/day without any dose-limiting toxicities observed.

The combination of AA with mFOLFOX6 or FOLFIRI showed promising preliminary efficacy, with an objective response rate of 58.3% and a disease control rate of 95.8%, indicating that this treatment could be a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. Wang, F., He, MM., Wang, ZX., et al.[2022]

High doses of Vitamin C and Vitamin B3 can selectively induce cell death in colorectal cancer stem cells (CSCs) with BRAF and KRAS mutations, showing a potential therapeutic effect for advanced colorectal cancer.

At low doses, both vitamins promote the proliferation of CSCs without affecting non-stem cancer cells, highlighting the importance of dosage in cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs). Sen, U., Shenoy P, S., Bose, B.[2018]

In a 4-year chemoprevention trial involving 58 patients with familial adenomatous polyposis, the combination of vitamin C and vitamin E was tested for its effects on rectal polyps, showing limited impact from high-fiber supplements when analyzed by intent to treat.

However, when accounting for patient compliance, the high-fiber supplement demonstrated a stronger benefit in reducing rectal polyps during the middle two years of the trial, suggesting that dietary grain fiber may help inhibit the development of benign large bowel neoplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. DeCosse, JJ., Miller, HH., Lesser, ML.[2019]

Bioactive Food Components (BFCs) found in fruits and vegetables have shown both chemopreventive and anti-tumor properties in colorectal cancer (CRC), suggesting they can play a significant role in cancer prevention and treatment.

BFCs may enhance the effectiveness of conventional cancer treatments, but their clinical use is limited by challenges related to bioavailability and the complexity of their effects, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioactive food components for colorectal cancer prevention and treatment: A good match. Amintas, S., Dupin, C., Boutin, J., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study). [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Current strategies in previously untreated advanced colorectal cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Colorectal cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs). [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Bioactive food components for colorectal cancer prevention and treatment: A good match. [2023]