The goal of this study is to determine if an alternative cabozantinib dosing regimens results in a similar drug exposure compared to the standard regimens in patients with metastatic renal cell carcinoma (mRCC). All dosages of cabozantinib (20 ,40, 60mg) have the same price, and cabozantinib is eliminated very slowly by the body. This means that using fewer tablets could potentially lead to cost savings, while remaining equally effective.

The main questions it aims to answer are:

• Is the drug exposure from our experimental regimens similar to the standard dosing regimens?
• Do the experimental regimens affect the number of side effect and the patients' quality of life?

Participants will:

• Take cabozantinib according to either the experimental or standard dosage regimen for 4 weeks
• After 4 weeks: visit the clinic to collect some blood samples and complete two questionnaires.
• 1 and 3 days after this visit: visit the clinic to collect 1 blood sample.
• The day after the hospital visit: switch to the other dosing regimen and according to that regimen for another 4 weeks.
• After 4 weeks: visit the clinic to collect some blood samples and complete two questionnaires
• 1 and 3 days after this visit: visit the clinic to collect 1 blood sample.

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.

To be determined in detail