Observational study of the effects of probenecid on the metabolism and working mechanism of sorafenib (PROSORA-study)

Phase 1

• Conditions: patients with unresectable hepatocellular cancer, advanced clear-cell renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002470-40-NL
• Lead Sponsor: Erasmus MC Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-16
• Last Update Posted: 11 December 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 16

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 studyNB. 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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified