Cabozantinib Dose Skipping as an Alternative to Dose Reductions

Standard regimens: 20 or 40mg once daily with standard breakfast

Experimental regimens:

• Instead of 20mg once daily: 60mg for one day, followed by two skipping days (60-0-0). Also taken with standard breakfast.
• Instead of 40mg once daily: 60mg for two days, followed by one skipping day (60-60-0). Also taken with standard breakfast.

Inclusion criteria

• Willing and able to provide informed consent;
• Aged 18 years or older;
• Histologically confirmed advanced renal cell carcinoma;
• At least 4 weeks on a stable dosage of cabozantinib of 40 mg or 20 mg once daily as single-agent treatment or in combination with nivolumab;
• Acceptable tolerability and the need for dose reductions or treatment interruptions has been estimated as low;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Estimated life expectancy of ≥6 months;
• No response evaluation planned during the study period.

Exclusion criteria

• Inability to follow the recommended standard breakfast;
• Gastrointestinal abnormalities influencing the absorption of cabozantinib, including active inflammatory bowel disease, malabsorption syndrome, and prior major surgery of the stomach, pancreas, liver or small bowel.
• Use of moderate or strong inhibitor of cytochrome P450 enzymes within 1 month of start of treatment with cabozantinib, including ketoconazole, grapefruit juice, clarithromycin, erythromycin, itraconazole and ritonavir.
• Use of moderate or strong inducer of cytochrome P450 enzymes within 1 month of start of treatment with cabozantinib, including rifampicin, phenytoin, carbamazepine, phenobarbital and herbal preparations containing St. John's Wort.
• Use of inhibitor of multidrug resistance-associated protein 2 within 1 month of start of treatment with cabozantinib, including cyclosporine, delavirdine, efavirenz, emtricitabine, benzbromarone and probenecid.