The Influence of Phenotype, Grapefruit Juice and Orange Juice on the Pharmacokinetics of Sunitinib in Cancer Patients

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

In this prospective pharmacokinetic we investigate the following topics:

• The influence of grapefruit juice and orange juice on the steady-state pharmacokinetics of sunitinib in cancer patients

• The influence of sunitinib on the pharmacokinetics of midazolam in cancer patients

• The relationship between Cytochrome-P450-3A4 (CYP3A4) phenotype, as assessed using the midazolam clearance test, and the steady-state pharmacokinetics of sunitinib in cancer patients

• The effect of grapefruit juice and orange juice on CYP3A4 metabolism

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Leiden University Medical Center
• Treatments: Midazolam; Sunitinib

Criteria

Inclusion Criteria:

• Patients with imatinib-resistant gastro-intestinal stromal cell tumor or metastatic renal cell carcinoma treated with sunitinib at a dose level of 25-50 mg sunitinib per day in a 4 weeks on/2 weeks off schedule.

• Age at least 18 years

• WHO performance status < 2.

• At least 4 weeks since last chemotherapy, hormonal, or radiation therapy.

• A life expectancy of at least 12 weeks.

• Patients must have an adequate functional reserve as defined by: hemoglobin > 6.0 mmol/L, White Blood Count > 3.0 x 109/L, neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, creatinine clearance > 60 mL/min, bilirubin within normal limits, Alanine transaminase and aspartate transaminase < 2.5 times the upper limit of normal (unless due to liver metastases, then < 5 times the upper limit of normal.

• Written informed consent.

Exclusion Criteria:

• Patients with hematological malignancies

• Concurrent other chemotherapy, immunotherapy, or radiotherapy.

• Concurrent use of other substances known or likely to interfere with the pharmacokinetics of sunitinib (e.g., ketoconazole, cyclosporine A).

• Use of drugs, herbal preparations and/or dietary supplements known to influence the expression of CYP3A (e.g., phenytoin, rifampicin, St. John's wort, garlic supplements, milk thistle) within the preceding 2 weeks.

• Present clinical signs of symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan. A patient with brain and/or leptomeningeal metastases may be included only if he/she is asymptomatic on neurological examination and is not receiving corticosteroid therapy to control symptoms.

• Patients with uncontrolled infection.

• Concurrent severe medical problems unrelated to the malignancy that would limit full compliance with the study or expose the patient to extreme risk.

• Patients with pre-existing cardiac disease, including clinical congestive heart failure, cardiac arrhythmias requiring treatment, or a myocardial infarction within the preceding 3 months.

• Patients who have received another investigational drug within 30 days or 5 half-lives prior to entry in the study (whichever is longer).

• History of allergic reaction to compounds chemically related to sunitinib.

• Patients who are pregnant or breastfeeding.

• Patients of childbearing potential, not practicing adequate contraception.

• Patients that are unable to ingest oral medication and/or are known with gastric emptying disorders.