Taking cabozantinib on a skip-days schedule instead of lowering the daily dose

Cabozantinib Dose Skipping as an Alternative to Dose Reductions

This test tries whether taking cabozantinib on a skip-days schedule gives similar drug levels, side effects, and quality of life for adults with metastatic renal cell carcinoma who are already on 20–40 mg daily.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Leiden University Medical Center (Academic / other)
• Drugs / interventions: nivolumab, cabozantinib
• Locations: 1 site (Leiden, South Holland)
• Trial ID: NCT07077161 on ClinicalTrials.gov

What this trial studies

Adults with metastatic renal cell carcinoma who are stable on 20 mg or 40 mg daily cabozantinib will follow either the standard daily dosing or an experimental skip-days schedule for four weeks. The experimental schedules use 60 mg on one or two days followed by one or two days off (60-0-0 or 60-60-0), while standard dosing remains 20 mg or 40 mg once daily with a standard breakfast. Blood samples collected after four weeks and at 1 and 3 days post-visit will be used to compare pharmacokinetic exposure, and patients will complete questionnaires about side effects and quality of life. The study aims to determine whether similar drug exposure can be achieved with fewer tablets while monitoring tolerability and patient-reported outcomes.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed advanced renal cell carcinoma who have been on a stable 20 mg or 40 mg daily cabozantinib regimen for at least four weeks, have ECOG performance status 0–2, expected survival ≥6 months, and can follow the required breakfast and clinic visits.

Not a fit: Patients with gastrointestinal disorders affecting absorption, recent use of moderate/strong CYP inhibitors, inability to follow the required breakfast, or those needing imminent dose reductions or planned response evaluations are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, patients could achieve similar drug exposure with fewer tablets, potentially lowering cost and maintaining or improving tolerability.

How similar studies have performed: The skip-day dosing concept is relatively novel for cabozantinib with limited direct clinical data, though pharmacokinetic principles and experience with other long half-life drugs offer some supportive rationale.

Eligibility criteria

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.

Where this trial is running

Leiden, South Holland

• Lumc — Leiden, South Holland, Netherlands (Recruiting)

Study contacts

• Principal investigator: Tom van der Hulle, MD PhD — Leiden University Medical Center
• Study coordinator: Tom van der Hulle, MD PhD

Conditions Renal Cell Carcinoma; RCC; Cabozantinib; pharmacokinetics