Botensilimab + Balstilimab and Diet + Vitamin C for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byDiana Hanna, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Southern California
Must not be taking: Diabetes medications, Oral vitamin C
Disqualifiers: Diabetes, Autoimmune disease, Uncontrolled illness, others
No Placebo Group
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.
12345What 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.
15678Eligibility 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
+14 more
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.
+17 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (botensilimab, balstilimab, FMD, vitamin C)Experimental Treatment7 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Los Angeles General Medical CenterLos Angeles, CA
USC / Norris Comprehensive Cancer CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
University of Southern CaliforniaLead Sponsor
National Cancer Institute (NCI)Collaborator
References
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]To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC).
Current strategies in previously untreated advanced colorectal cancer. [2018]Colorectal cancer is the second most common cause of cancer-related death in the United States. Approximately 30% to 40% of patients with colorectal cancer have locoregionally advanced or metastatic disease on presentation and cannot be cured with surgical therapy. After many years without significant change, systemic therapy for colorectal cancer is rapidly evolving. The past decade has seen the introduction of new chemotherapeutic agents such as irinotecan (Camptosar), oxaliplatin (Eloxatin) and the oral 5-FU prodrug capecitabine (Xeloda). Combination studies of these new agents with the standard 5-FU/leucovorin have extended median survival in patients with advanced colorectal cancer for up to 21 months. In addition, targeted agents with activity in colorectal cancer have emerged and are promising. This article reviews the current treatment recommendations for patients who present with advanced colorectal cancer. Survival in patients with advanced colorectal cancer is on a positive trajectory. The hope that some patients with advanced disease will be long-term survivors (even without surgery) appears to be within the range of possibility.
Colorectal cancer. [2023]Cancers of the colon and rectum will affect 1 in 17 North Americans during their lifetime. The progress witnessed in the treatment of these cancers in recent years has been remarkable. Improvements have been realized in surgical technique, radiation therapy, and systemic therapies, particularly with the addition of oxaliplatin and irinotecan to the previously limited armamentarium of fluorouracil alone. Targeted therapies directed at the vascular endothelial growth factor pathway and the epidermal growth factor pathway are now key players in the treatment of colorectal cancer. With current-day therapies, more than 75% of patients with localized disease are recurrence free at 3 years, and up to 50% of patients with advanced unresectable disease are alive at 2 years. This review focuses on the evidence supporting the current role of chemotherapy and radiation therapy in the adjuvant management of colorectal cancers and the strategy of combining chemotherapy and biological therapy in the treatment of metastatic disease.
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]To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.
Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. [2022]Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC).
Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs). [2018]Colorectal cancer is one of the global causes of cancer deaths. Cancer stem cells (CSCs) inside the tumour niche responsible for metastasis and relapses, and hence need to be targeted for cancer therapeutics. Although dietary fibre and lifestyle changes have been recommended as measures for colorectal cancer prevention, no such recommendations are available for using water soluble vitamins as prophylaxis measure for colorectal cancers. High dose of Vitamin C has been proven to selectively kill colon cancer cells having BRAF and KRAS mutations by inducing oxidative stress. In this study, we show for the first time the opposing effects of the low and high dose of Vitamin C and vitamin B3 on colon CSCs isolated from HT-29 and HCT-15 colorectal carcinoma cell lines. At small doses, both of these vitamins exerted a cell proliferative effect only on CSCs, while there was no change in the proliferation status of non-stem cancer cells and wild-type (WT) populations. On the other hand, the death effects induced by high doses of Vitamin C and B3 were of the order of 50-60% and ∼30% on CSCs from HT-29 and HCT15, respectively. Interestingly, the control fibroblast cell line (NIH3T3) was highly refractory all the tested concentrations of Vitamin C and B3, except for the highest dose - 10,000 μg of Vitamin C that induced only 15% of cell death. Hence, these results indicate the future scope of use of therapeutic doses of Vitamin C and B3 especially in patients with advanced colorectal cancer.
Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. [2019]Over a 4-year period in a chemoprevention trial on large bowel neoplasia, 58 patients with familial adenomatous polyposis were treated with 4 g of ascorbic acid (vitamin C)/day plus 400 mg of alpha-tocopherol (vitamin E)/day alone or with a grain fiber supplement (22.5 g/day). In this randomized, double-blind, placebo-controlled study, we determined the effects of these supplements on rectal polyps in these patients. Analysis by intent to treat suggested that the high-fiber supplement had a limited effect. Analysis adjusted for patient compliance showed a stronger benefit from the high-fiber supplement during the middle 2 years of the trial. The results provide evidence for inhibition of benign large bowel neoplasia by grain fiber supplements in excess of 11 g/day in this study population. The findings are consistent with the hypothesis that dietary grain fiber and total dietary fat act as competing variables in the genesis of large bowel neoplasia.
Bioactive food components for colorectal cancer prevention and treatment: A good match. [2023]Colorectal cancer (CRC) is the third most frequent cancer worldwide, accounts for about 10% of the total cancer cases, and ranks as the second cause of death by cancer. CRC is more prevalent in developed countries in close causal relation with occidental diets. Due to anatomy, the diet has a strong impact on CRC. High contents in meat are acknowledged risk factors whereas a diet rich in fruits and vegetables is an established CRC protective factor. Fruits and vegetables contain numerous Bioactive Food Components (BFCs), physiologically active food compounds, beneficial on health. Preventive and therapeutic benefits of BFCs in cancer have increasingly been reported over the past 20 years. BFCs show both chemopreventive and anti-tumor properties in CRC but more interestingly, abundant research describes BFCs as enhancers of conventional cancer treatments. Despite these promising results, their clinical transferability is slowed down by bioavailability interrogations and their poorly understood hormetic effect. In this review, we would like to reposition BFCs as well-fitted for applications in CRC. We provide a synthetic overview of trustworthy BFC applications in CRC, with a special highlight on combinatory approaches and conventional cancer treatment potentiation strategies.