Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients With KRAS-Mutant Metastatic Colorectal Cancer

Stage IV Colorectal Cancer AJCC v8 Clinical Trial

Official title: A Phase Ib Study of Botensilimab Plus Balstilimab and Fasting-Mimicking Diet (FMD) Plus Vitamin C in Patients With KRAS-Mutant Metastatic Colorectal Cancer

Status Not yet recruiting

Clinical Trial Summary

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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of the fasting mimicking diet (FMD) when combined with vitamin C and botensilimab plus balstilimab by determining the proportion of patients who adhere to the FMD ≥ 75% of the designated days and receive all doses of botensilimab, balstilimab and Vitamin C for at least any two cycles of therapy.

II. To characterize the safety and tolerability of FMD and vitamin C when combined with botensilimab and balstilimab by assessing any grade toxicities per Common Terminology Criteria for Adverse Events (CTCAE) 5.0.

SECONDARY OBJECTIVES:

I. To obtain a preliminary assessment of anti-tumor activity of botensilimab plus balstilimab and FMD plus vitamin C by determining the overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To estimate the progression-free and overall survival in patients with KRAS-mutant colorectal cancer (CRC) receiving botensilimab plus balstilimab and FMD plus vitamin C.

EXPLORATORY OBJECTIVES:

I. To characterize circulating tumor deoxyribonucleic acid (ctDNA) and ctDNA methylation (TET, Wnt, JAK/STAT, PI3K/AKT, CXCR, ALDH, AMPK) profiles at baseline, on treatment and at disease progression.

II. To examine metabolomic markers (IGF-1, GAPDH, DHA, GLUT-1, iron signaling) at baseline, on treatment and at disease progression.

OUTLINE:

Patients receive botensilimab intravenously (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, computed tomography (CT) scans and magnetic resonance imaging (MRI) throughout the study.

After completion of study intervention, patients are followed up at 30 days and every 3 months for up to 6 months. ;

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Adenocarcinoma
• Stage IV Colorectal Cancer AJCC v8

• NCT number: NCT06336902
• Study type: Interventional
• Source: University of Southern California
• Contact: Charlean Ketchens, RN
• Phone: 323-865-0451
• Email: Charlean.Ketchens@med.usc.edu
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 1, 2024
• Completion date: July 1, 2027