|- candidate number||28476|
|- NTR Number||NTR6967|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||22-jan-2018|
|- Secondary IDs||MEC 17-490 METC Erasmus MC|
|- Public Title||The influence of probenecid on the metabolism of sorafenib|
|- Scientific Title||A study of the effects of probenecid on the pharmacokinetics and pharmacodynamics of sorafenib (PROSORA-study)|
|- hypothesis||We want to determine the influence and safety of probenecid on sorafenib pharmacokinetics. By inhibiting the OAT6 transporter there might be a faborable effect on Hand-foot syndrome|
|- Healt Condition(s) or Problem(s) studied||Hepatocellular carcinoma, Renal cell carcinoma, Thyroid carcinoma|
|- 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 but nog longer than 14 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).
|- 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
8. A BMI (body mass index) of less than 8.5 and more than 35.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||27-nov-2017|
|- planned closingdate||1-jun-2019|
|- Target number of participants||16|
|- Interventions||sorafenib alone vs sorafenib + probenecid for 14 consecutive days|
|- Primary outcome||To demonstrate 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 outcome||1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), Maximum steady-state concentration (Cmaxss), Minimal concentration (Cmin), steady-state volume of distribution (Vss) and half-life (t˝)).|
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.
4. To determine the influence of HFSR on quality of life
|- Timepoints||Pharmacokinetics and skin-biopsies will be taken at day 1 and day 15. Also an HFSR QoL questionnaire will be taken out at registration, day 1 and day 15. |
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| Koen (G.A.M.) Hussaarts|
|- CONTACT for SCIENTIFIC QUERIES|| Koen (G.A.M.) Hussaarts|
|- Sponsor/Initiator ||Erasmus Medical Center|
(Source(s) of Monetary or Material Support)
|Erasmus Medical Center|
|- Brief summary||In this study we want to determine the safety and influence on pharmacokinetics of sorafenib by probenecid. As a secondary outcome we study the influence on HFSR. |
|- Main changes (audit trail)|
|- RECORD||22-jan-2018 - 15-feb-2018|