The Pharmacological Effects of Using Cabozantinib With a Light Breakfast (Skippy 1)

December 14, 2023 updated by: dr. Tom van der Hulle

The Pharmacological Effects of Using Cabozantinib With a Light Breakfast: the Skippy 1 Study

Cabozantinib is a drug which is used to treat metastasized kidney cancer. While it works well, it has a lot of side effects and is quite expensive (€213,- every tablet, €6403,- every month). The standard recommended dose is 60 mg once a day, taken in fasted state. This means patients are not allowed to eat at least 2 hours before and one hour after taking cabozantinib. In daily practice, this is difficult for patients. It might be that by taking with breakfast the chance of side effects like nausea and diarrhea decreases. If patients take cabozantinib with breakfast, the body will have a higher uptake of the drug.

Often the dose of cabozantinib has to be lowered due to side effects. All tablets cabozantinib have the same price, despite how many milligrams are in the tablets. Cabozantinib stays in the body for a long time after ingestion. It takes approximately 120 hours before half of the medicine has left the body. This means it might not be necessary to take cabozantinib every day. Therefore, it is interesting to investigate if taking cabozantinib with breakfast makes it possible to skip taking cabozantinib once in a while. In this study, the investigators want to investigate to what extent the exposure of cabozantinib increases after ingestion with a light breakfast. The results from this study will be used for the development of alternative dosing regimens with cabozantinib tablets of 60 mg taken with a light breakfast including skipping days.

In this study, patients will randomized to start with taking cabozantinib in fasted state (standard regimen) and taking cabozantinib with a light breakfast (experimental regimen). Menu options will be provided. After at least 4 weeks taking cabozantinib according to the randomized regimen, patients will be submitted to the hospital for one day to measure the amount of cabozantinib in the blood at several points of time. This will be measured by venepuncture and fingerprick microsampling. When all blood samples have been collected, the patient will switch to the other regimen. After at least 4 weeks taking cabozantinib according to the second regimen, venous blood samples will be collected in exactly the same way. After all patients have completed the study, an analysis will be performed to determine the change in exposure to cabozantinib when it is taken with a light breakfast. The results will be used in order to determine the definitive experimental dosing regimens that will be investigated a subsequent study. Patients will be monitored for side effects, especially nausea and/or diarrhea.

The primary goal is to investigate to what extent the exposure of cabozantinib increases by taking cabozantinib with a light breakfast compared to taking cabozantinib in fasted state. The secondary objective is to investigate the analytical feasibility of microsampling (finger prick) for cabozantinib concentration measurements and to monitor side effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Zuid-Holland
      • Leiden, Zuid-Holland, Netherlands, 2333 ZA
        • Recruiting
        • Leids Universitair Medisch Centrum
        • Contact:
        • Contact:
        • Principal Investigator:
          • Tom van der Hulle, MD PhD
      • Rotterdam, Zuid-Holland, Netherlands, 3015 GD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Willing and able to provide informed consent;
  • Aged 18 years or older;
  • Histologically confirmed advanced renal cell carcinoma;
  • Receiving cabozantinib as monotherapy as treatment for RCC;
  • At least 4 weeks on a stable dosage of cabozantinib;
  • 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;
  • Cabozantinib trough concentration ≤1125 ng/ml in steady state

Exclusion Criteria:

  • Inability to follow the recommended light breakfast;
  • 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.
  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard regimen
Patients will continue to use cabozantinib in fasted state, as part of standard of care, in the recommended dose as prior to enrollment in the study.
Experimental: Experimental regimen
Patients will take the prior recommended dose cabozantinib with a light breakfast.
Other: Light breakfast
Light breakfast, standardized by 7 menu options for patients. All breakfast options contain the same amount of fat (9-10 g). Example of a menu: 150 ml full-fat yoghurt, 40 gram muesli with sugar, 1 glass of tea.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the concentration-time curve (AUC)
Time Frame: At both hospital admissions after at least 28 days on the regimen (t = 0, 1, 2, 3, 4, 5, 6, 8 and 24 hours)
Increase of the area under the concentration-time curve (AUC) of the experimental regimen compared to the standard regimen
At both hospital admissions after at least 28 days on the regimen (t = 0, 1, 2, 3, 4, 5, 6, 8 and 24 hours)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: At inclusion and at both hospital admissions after at least 28 days on the regimen
The total number of patients experiencing (S)AEs
At inclusion and at both hospital admissions after at least 28 days on the regimen
Analytical feasibility
Time Frame: At both hospital admissions after at least 28 days on the regimen (t = 0, 1, 2, 3, 4)
Analytical correlation/agreement between venapuncture (plasma) measurements and microsampling (whole blood and capillary plasma) measurements
At both hospital admissions after at least 28 days on the regimen (t = 0, 1, 2, 3, 4)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

dr. Tom van der Hulle

Collaborators

Leiden University Medical Center

Investigators

  • Principal Investigator: Tom van der Hulle, MD PhD, Leiden University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 25, 2023

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

May 1, 2024

Study Registration Dates

First Submitted

February 11, 2022

First Submitted That Met QC Criteria

February 22, 2022

First Posted (Actual)

March 2, 2022

Study Record Updates

Last Update Posted (Estimated)

December 20, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 81846

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

To be determined in detail

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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