Assistant Professor University of Alabama at Birmingham, AL, United States
Background: Acarbose is a pseudo-tetra saccharide of bacterial origin and an orally active alpha glucosidase inhibitor that delays the digestion and absorption of ingested complex carbohydrates. Consumption of Acarbose leads to a higher fraction of complex carbohydrates passing through the lower gut. Studies have previously demonstrated increases in species such as Bifidobacterium in gut flora linked with acarbose consumption. Emerging evidence suggests that the gut microbiome may be linked to improved response or acquired resistance to immune checkpoint blockade, and may also have an independent effect on tumor proliferation. We hypothesize that Acarbose may thus improve the outcomes in patients treated with immune checkpoint inhibitors or immunogenic tumor subtypes while being tolerable for patients. We thus designed a pilot study to evaluate the safety of feasibility of combining acarbose with standard of care (SOC) therapy in renal cell carcinoma patients.
Methods: In this open label, single arm, single-center pilot study, adult patients with advanced/metastatic clear cell or non-clear cell renal cell carcinoma are eligible. An estimated 24 patients will be enrolled. Patients treated with all immunotherapy based standard of care regimens will be included. Acarbose will be dosed as 25 mg PO three times a day continuously with escalation based on clinical tolerance to 100 mg PO three times a day. Study treatment continues until RECIST 1.1 disease progression or other discontinuation criteria are met. The co primary endpoints are safety as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE v.6.0) and changes in specific bacterial species in the gut flora. Secondary endpoints include estimated median progression free survival and overall survival of patients treated with SOC+Acarbose
