Cabozantinib Dose Skipping as an Alternative to Dose Reductions
ConditionRenal Cell Carcinoma (RCC)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
Sponsordr. Tom van der Hulle
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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.
Trial design
Design model
Crossover
Treatments tested in this trial
Cabozantinib
DrugFor patients using 40mg the experimental regimen consists of 60mg once daily for 2 days followed by 1 skipping day (60-60-0 mg). For patients using 20mg the experimental regimen consists of 60mg once daily for 1 day followed by 2 skipping days (60-0-0 mg). In both cases cabozantinib is also taken with standard breakfast.
Treatment groups
34 Participants
are divided into 1 treatment groupGroup A: Standard regimenActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Comparison of the AUC0-72h of the experimental and the standard regimen.
AUC is calculated by modeliing a PK curve from plasma concentrations. AUCs are compared between the standard and experimental regimen.
Time frame
From enrollment to the end of the study at approximately 2 months2
Comparison of blood trough concentration (Ctrough)
Comparison of Ctrough, which is the plasma concentration of cabozantinib before ingestion of a dose cabozantinib, between the standard and experimental regimen.
Time frame
From enrollment to the end of the study at approximately 2 monthsSecondary outcomes
1
Health-economic cost-consequences
Calculating the cost-savings of the alternative dosing regimens
Time frame
From enrollment to the end of the study at approximately 2 months2
Patients preference
Patients preference of one of the dosing regimens.
Time frame
From enrollment to the end of the study at 2 months3
Quality of life score
Fill in a questionnaires (EQ-5D-5L) about the quality of life. Which looks into two things: 1. Five dimensions of health: mobility, self-care, daily activities, pain/disconfomrt and anxiety/some feelings. It uses a five point scale with 1 equally to no problem and 5 equally to extreme problems. It results in a score with 0 equally to dead and 1 equally to perfect health. 2. Subjective assessment of one's own health on a scale from 0 to 100. Where 0 equals worst imaginable health and 100 equals best imaginable health.
Time frame
From enrollment to the end of the study at approximately 2 months4
Quality of life score
Fill in a questionnaire (FKSI-19) with questions reflecting quality of life in patients with RCC. A question is answered using a 5-point scale where zero equals not at all and 4 equals very much. The higher the score the better the quality of life.
Time frame
From enrollment to the end of the study at approximately 2 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
dr. Tom van der Hulle
Lead sponsor
Leiden University Medical Center
Sponsor institution
Source ClinicalTrials.gov