Adverse events (AEs) with Cabozantinib are frequent (about 40-67% of patients) and often lead to temporary treatment interruptions, dose reductions or permanent discontinuations, potentially reducing dose intensity and sustained exposure. Therefore, strategies are needed to improve tolerability without compromising antitumor activity. Therapeutic drug monitoring (TDM) is particularly suitable for drugs with high interpatient variability, narrow therapeutic windows and defined exposure-response relationships; real world data support this profile for Cabozantinib and suggest that pharmacokinetically guided dosing could help manage toxicity while maintaining efficacy. Based on this evidence, the study proposes a model of individualized pharmacological counselling integrating TDM, pharmacogenetic testing and structured evaluation of pharmacological interactions to optimize Cabozantinib exposure and minimize avoidable toxicity.
Patients diagnosed with histologically confirmed advanced/metastatic RCC with predominantly clear cell subtype.
Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC, candidate to receive systemic treatment with nivolumab + Cabozantinib or Cabozantinib monotherapy as per clinical practice (investigators choice).
Signed Written Informed Consent.
Male or female subjects aged ≥18 years old.
Patients with non-renal cell neoplasms of the kidney (e.g. urothelial, sarcoma, lymphoma).
Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low-grade prostate cancer (≤pT2, N0; Gleason 6) with no plans for treatment intervention.
Pregnancy status.
Refusal of informed consent.
Single group
Intensified Monitoring of Pharmacology
Other interventionindividualized pharmacological counselling integrating TDM, pharmacogenetic testing and structured evaluation of pharmacological interactions
Impact of the systematic pharmacological counseling activity intervention on Cabozantinib related toxicity
The impact will be evaluated as the overall change of the frequency of treatment interruptions due to clinically relevant toxicity in RCC (Renal cell carcinoma) patients treated with Cabozantinib, compared to historical data.
Attitude Towards Pharmacological Counseling Among Oncologists
Rate of adherence to pharmacological counseling recommendations.
Validate LC-MS/MS methods for Cabozantinib quantification in plasma and dried blood spot (Capitainer B and Hemaxis) in terms of accuracy
Accuracy will be evaluated as difference between results obtained by the method to the nominal concentration of the analyte in the biological matrix
Validate LC-MS/MS methods for Cabozantinib quantification in plasma and dried blood spot (Capitainer B and Hemaxis) in terms of precision
Precision will be evaluated as Coefficient of Variation (CV) calculated as standard deviation/mean values
Validate LC-MS/MS methods for Cabozantinib quantification in plasma and dried blood spot (Capitainer B and Hemaxis) in terms of linearity
Linearity will be evaluated using squared R to assess the goodness of fit of the calibration curve
Click on the lead sponsor to view all of their trials.
