patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.
Conditions
Interventions
Trade Name: Sorafenib
Pharmaceutical Form: Tablet
Trade Name: Probenecid
Product Name: Probenecid
Product Code: M04AB01
Pharmaceutical Form: Tablet
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Histological or cytological confirmed diagnosis of mRCC, HCC or differentiated thyroid carcinoma 3. Start of sorafenib therapy, at least 7 days prior to start of the study NB. Patients are allowed to have had previous sorafenib therapy or have started with sorafenib. 4. WHO Performance Status = 2 (appendix D) 5. Able and willing to sign the Informed Consent Form prior to screening evaluations 6. Adequate organ function as defined by: a. Total bilirubin = 1.5 x ULN (except in case of documented Gilbert’s disease) b. ASAT = 3.0 x ULN (or = 5 x ULN if liver metastases are present) c. ALAT = 3.0 x ULN (or = 5 x ULN if liver metastases are present) d. Serum creatinin = 1.5 x ULN 7. Adequate baseline patient characteristics (complete blood count, and serum biochemistry which involves sodium, potassium, creatinin, calculation of creatinin clearance (MDRD), amylase, lipase, calcium, phosphate, AST, ALT, gamma glutamyltranspeptidase (?-GT), lactate dehydrogenase (LDH), ALP, total bilirubin, albumin). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Use of drugs which may show an increased systemic exposure when taken concomitantly with probenecid. (see appendix C) 2. Patients with known blood dyscrasias, uric acid kidney stones or until an acute gouty attack has subsided. 3. Use of (over the counter) medication or (herbal) supplements which can interact with either sorafenib or probenecid, e.g. by induction or inhibition of CYP3A4, UGT1A9 (see appendix B and C) 4. Unable or unwilling to abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study 5. Previous use of probenecid during the last 2 weeks prior to sorafenib treatment 6. Contraindications for use of probenecid such as acute gouty attack or porphyria. 7. Unwilling to undergo a skin biopsy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the bioequivalence of sorafenib with probenecid relative to sorafenib without probenecid based on the AUC in patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.;Secondary Objective: 1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), Minimal concentration (Cmin), steady-state volume of distribution (Vss) and half-life (t½)). 2. To evaluate the incidence and severity of side-effects of treatment with sorafenib in absence and presence of probenecid (in particular HFSR) . 3. To evaluate the intracellular concentration of sorafenib in skin in patients treated with sorafenib in absence and presence of probenecid. ;Primary end point(s): To demonstrate the bioequivalence of sorafenib with probenecid relative to sorafenib without probenecid based on the AUC in patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: End of study;Secondary end point(s): 1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), Minimal concentration (Cmin), steady-state volume of distribution (Vss) and half-life (t½)). 2. To evaluate the incidence and severity of side-effects of treatment with sorafenib in absence and presence of probenecid (in particular HFSR) . 3. To evaluate the intracellular concentration of sorafenib in skin in patients treated with sorafenib in absence and presence of probenecid. | — |
Countries
Netherlands
Contacts
Public ContactRon Mathijssen
Erasmus MC
Outcome results
None listed