The skippy 1 study

Ziekenhuizen

• Erasmus Medisch Centrum Rotterdam
• Leids Universitair Medisch Centrum

Doel van het onderzoek

• Area under the concentration-time curve (AUC) [ Time Frame: Phase A: at both hospital admissions after at least 28 days on the regimen (t = 0, 1, 2, 3, 4, 5, 6, 8 and 24 hours) ]Increase of the area under the concentration-time curve (AUC) of the experimental regimen compared to the standard regimen
• Area under the concentration-time curve (AUC) [ Time Frame: Phase B: at both hospital admissions after at least 28 days on the regimen (t = 0, 1, 2, 3, 4, 5, 6, 8 and 24 hours, plus 96 hours if original dose of 60 mg daily) ]The comparison of the AUC of the experimental and the standard regimen.

Behandeling

• No Intervention: Standard regimenPatients will continue to use cabozantinib in fasted state, as part of standard of care, in the recommended dose as prior to enrollment in the study.
• Experimental: Experimental regimenIn phase A of the study, patients will take the prior recommended dose cabozantinib with a continental breakfast. In phase B of the study, patients will take 60 mg tablets with a continental breakfast, the frequency depending on their original dose in the standard regimen.Interventions:
  • Other: Continental breakfast
  • Other: Changing dose interval

Belangrijkste in/exclusiecriteria

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;
• 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;

In order to be eligible to participate in phase A of the study, a subject must meet an additional criterium:

- Cabozantinib trough concentration ≤1125 ng/ml in steady state

Exclusion Criteria:

• Inability to follow the recommended continental breakfast;
• Gastro-intestinal abnormalities influencing the absorption of cabozantinib, including active inflammatory bowel diseases, malabsorption syndrome and prior major surgery of the stomach, pancreas, liver or smaller bowel.
• Use of moderate or strong inhibitor of cytochrome P450 enzymes within 1 month of start of treatment with cabozantinib, including ketoconazole, grape fruit 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.

Contactpersoon

LUMC Tom van der Hulle