Cabozantinib Dose Skipping as an Alternative to Dose Reductions

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Cabozantinib
  For 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.

Первичные конечные точки

• Comparison of the AUC0-72h of the experimental and the standard regimen. [Срок оценки: From enrollment to the end of the study at approximately 2 months]
• Comparison of blood trough concentration (Ctrough) [Срок оценки: From enrollment to the end of the study at approximately 2 months]

Вторичные конечные точки (5)

• Health-economic cost-consequences [Срок оценки: From enrollment to the end of the study at approximately 2 months]
• Patients preference [Срок оценки: From enrollment to the end of the study at 2 months]
• Quality of life score [Срок оценки: From enrollment to the end of the study at approximately 2 months]
• Quality of life score [Срок оценки: From enrollment to the end of the study at approximately 2 months]
• Side effects: nausea and/or diarrhea [Срок оценки: From enrollment to the end of the study at approximately 2 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• LUMC — Leiden

Публикации

• Tan Z, Voller S, Yin A, Rieborn A, Gelderblom AJ, van der Hulle T, Knibbe CAJ, Moes DJAR. Population Pharmacokinetics of Cabozantinib in Metastatic Renal Cell Carcinoma Patients: Towards Drug Expenses Saving Regimens. Clin Pharmacokinet. 2024 Jun;63(6):857-869. doi: 10.1007/s40262-024-01379-y. Epub 2024 Jun 14. PMID 38874883

Идентификаторы

NCT: NCT07077161 · SKIPPY2 · 2025-522962-58-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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