SKIPP2: Cabozantinib Dose Skipping as an Alternative to Dose Reductions

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Jan 2026 → ongoing

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

- To demonstrate a comparable exposure to cabozantinib when taking cabozantinib 60 mg with a standard breakfast for 2 days followed by 1 skipping day compared to cabozantinib 40 mg o.d. in a fasted state.
- To demonstrate a comparable exposure to cabozantinib when taking cabozantinib 60 mg with a standard breakfast for 1 day followed by 2 skipping days compared to cabozantinib 20 mg o.d. in a fasted state.

Secondary objectives 1

1. - To investigate whether patients prefer to use cabozantinib with food or in a fasted state. - To investigate whether taking cabozantinib according to the alternative dosing schedules impacts the toxicity profile and health-related QoL. - To investigate the potential cost reduction that can be achieved by taking cabozantinib according to the alternative dosing schedules.

Conditions and MedDRA coding

Renal cell carcinom

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Willing and able to provide informed consent
2. Aged 18 years or older
3. Histologically confirmed advanced renal cell carcinoma
4. 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
5. Acceptable tolerability and the need for dose reductions or treatment interruptions has been estimated as low
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
7. Estimated life expectancy of ≥6 months
8. No response evaluation planned during the study period

Exclusion criteria 5

1. Inability to follow the recommended standard breakfast
2. 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
3. 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
4. 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
5. Use of inhibitor of multidrug resistance-associated protein 2 within 1 month of start of treatment with cabozantinib, including cyclosporine, delaviridine, efavirenz, emtricitabine, benzbromarone and probenecid

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Comparison of the area under the concentration-time curve (AUC0-72): calculated by modelling a pharmacokinetic curve from plasma concentrations cabozantinib, obtained by pharmacokinetic samples from 0 to 72 hours after ingestion of cabozantinib. The AUC0-72 of the standard and experimental regimen will be compared. It is defined as comparable if the geometric mean ratio is within the range of 0.8 – 1.25.
2. Comparison of the blood trough concentration (Ctrough): defined as the plasma concentration of cabozantinib before ingestion of a dose of cabozantinib. The Ctrough of the standard and experimental regimen will be compared. It is defined as comparable if the geometric mean ratio is within the range of 0.8 – 1.25.

Secondary endpoints 5

1. Health-care use: both medication use and hospitalisations will be registered from the patients’ hospital records
2. EQ-5D-5L Quality of Life (See Appendix 5): the EQ-5D-5L questionnaire will be taken after at least four weeks on treatment in the first part and after four weeks in the second part.
3. FKSI-19 Quality of Life (See Appendix 6): the FKSI-19 questionnaire will be taken after at least four weeks on treatment in the first part and after four weeks in the second part.
4. Adverse events: defined as any symptom, sign, illness, or untoward experience (including a clinically significant laboratory finding classified as Grade 3 or higher by the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) v5.0) (28) that develops or worsens during the course of the study, whether or not the event is considered related to study drug. Such an event should be recorded as an adverse event only after t
5. Percentage of patients preferring to take cabozantinib in fed state: Question whether patients would prefer to continue to take cabozantinib in fed state or to recommence taking cabozantinib in fasted state

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Tom v.d. Hulle

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Tom v.d. Hulle

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications