Renal Cell Carcinoma (RCC)Phase 2SKIPPY 2NCT07077161
Cabozantinib Dose Skipping as an Alternative to Dose Reductions
A Phase 2 study testing Cabozantinib in people with Renal Cell Carcinoma (RCC), run by dr. Tom van der Hulle at 1 site in Netherlands.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma (RCC)
- What is being tested?
- Cabozantinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteNetherlands
- Study dates
- 26 Jan 2026to 1 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
LUMC
Leiden, South Holland, 2333ZA
Tom van der Hulle, 0031715263464, t.van_der_hulle@lumc.nl
Nikki Kerssemakers, 0031683139525, n.kerssemakers@lumc.nl
About this study
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:
Read more
- 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.
Read the detailed description
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.
- Conditions
- Renal Cell Carcinoma (RCC)
- Being tested
- Cabozantinib
- Keywords
- Renal Cell Carcinoma, RCC, Cabozantinib, pharmacokinetics
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard regimen | Active comparator | taking 20mg or 40mg cabozantinib once daily with standard breakfast. Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment to the end of the study at approximately 2 months
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.
Measured: From enrollment to the end of the study at approximately 2 months
Secondary outcomes (5)
Health-economic cost-consequences
Calculating the cost-savings of the alternative dosing regimens
Measured: From enrollment to the end of the study at approximately 2 months
Patients preference
Patients preference of one of the dosing regimens.
Measured: From enrollment to the end of the study at 2 months
Quality of life score
Fill in a questionnaires (EQ-5D-5L) about the quality of life. Which looks into two things:
- 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.
- 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.
Measured: From enrollment to the end of the study at approximately 2 months
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.
Measured: From enrollment to the end of the study at approximately 2 months
Side effects: nausea and/or diarrhea
Total number of patients experiencing nausea and/or diarrhea
Measured: From enrollment to the end of the study at approximately 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2025
- Study start26 Jan 2026
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Cell Carcinoma (RCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- PK equivalence study
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- dr. Tom van der Hulle
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, dr. Tom van der Hulle, Leiden University Medical Center
- Investigators
- Tom van der Hulle, MD PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07077161
- Sponsor's protocol ID
- SKIPPY2
- Other IDs
- 2025-522962-58-00, 2025
- Acronym
- SKIPPY 2
- Status last verified
- Aug 2026
- First submitted
- 8 Jul 2025
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: To be determined in detail
Publications
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.
PubMed 38874883
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cabozantinib Dose Skipping as an Alternative to Dose Reductions
- ClinicalTrials.gov ID
- NCT07077161
- Acronym / sponsor ID
- SKIPPY 2 / SKIPPY2
- Conditions
- Renal Cell Carcinoma (RCC)
- Keywords
- Renal Cell Carcinoma, RCC, Cabozantinib, pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- dr. Tom van der HulleUniversity, hospital or other
- Study start
- 26 Jan 2026 (actual)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 22 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- PK equivalence study
| Arm | Type | Receives |
|---|---|---|
| Standard regimen | Active comparator | Drug: Cabozantinibtaking 20mg or 40mg cabozantinib once daily with standard breakfast. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabozantinibFor 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. | Drug | Standard regimen |
Primary outcome
Comparison of the AUC0-72h of the experimental and the standard regimen.
Time frame: From enrollment to the end of the study at approximately 2 months
AUC is calculated by modeliing a PK curve from plasma concentrations. AUCs are compared between the standard and experimental regimen.
Comparison of blood trough concentration (Ctrough)
Time frame: From enrollment to the end of the study at approximately 2 months
Comparison of Ctrough, which is the plasma concentration of cabozantinib before ingestion of a dose cabozantinib, between the standard and experimental regimen.
5 secondary outcomes
Health-economic cost-consequences
Time frame: From enrollment to the end of the study at approximately 2 months
Patients preference
Time frame: From enrollment to the end of the study at 2 months
Quality of life score
Time frame: From enrollment to the end of the study at approximately 2 months
Quality of life score
Time frame: From enrollment to the end of the study at approximately 2 months
Side effects: nausea and/or diarrhea
Time frame: From enrollment to the end of the study at approximately 2 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Results publication: PubMed 38874883Tan 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.
- Individual participant dataSharing planned: Undecided. To be determined in detail
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tom van der Hulle, MD PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib in people with Renal Cell Carcinoma (RCC), run by dr. Tom van der Hulle at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tom van der Hulle, MD PhD (0031715263464, t.van_der_hulle@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the AUC0-72h of the experimental and the standard regimen. (time frame: From enrollment to the end of the study at approximately 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07077161, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.