Onderzoek met hoge dosis sorafenib bij patiënten met solide tumoren gedoseerd op basis van de sorafenib bloedspiegels.
- Conditions
- advanced and metastasized solid malignancies, sorafenib, altered dosing schedule, dose titration, phase I study
- Registration Number
- NL-OMON23305
- Lead Sponsor
- VU University Medical Center
- Brief Summary
Honeywell R, Yarzadah K, Giovannetti E, et al. Simple and selective method for the determination of various tyrosine kinase inhibitors used in the clinical setting by liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878:1059-68.<br> -Pécuchet N, Lebbe C, Mir O, et al. Sorafenib in advanced melanoma: a critical role for pharmacokinetics? Br J Cancer. 2012;107:455-61.<br> -Strumberg D, Clark JW, Awada A, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist. 2007;12:426-37.<br> -Wang X, Zhang L, Goldberg SN, et al. High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma. J Transl Med. 2011;9:220. doi: 10.1186/1479-5876220.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 40
1. Histological or cytological documentation of incurable locally advanced or metastatic solid malignancy for which no standard therapy exists.
2. Patients eligible for the expansion cohort must be willing to undergo tumor and skin biopsies, while tumor and skin biopsies are optional for patients enrolled in the escalation cohort. Primary tumor or metastatic site must be accessible for biopsy. Bone metastases are excluded as a biopsy site.
1. Evidence of a significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture.
2. Prior radiotherapy in the abdominal or thoracic area or in > 3 vertebrae in the spine (if long interval since previous radiotherapy or radiotherapy in ¡Ü 3 vertebrae, eligibility will be decided on an individual basis by the primary investigator).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method -To determine the maximum tolerated sorafenib plasma AUC0-12h of high-dose sorafenib when administered in a weekly, pulsatile schedule.<br /><br>-To assess the safety and tolerability of high-dose, pulsatile sorafenib titrated on the target AUC0-12h.<br />
- Secondary Outcome Measures
Name Time Method Escalation cohorts:<br /><br>-To determine the pharmacokinetic behaviour of sorafenib and its major active metabolite pyridine N-oxide.<br /><br>-To determine a recommended phase II plasma sorafenib AUC0-12h.<br /><br>Expansion cohort:<br /><br>-Preliminary assessment of the efficacy of high-dose, pulsatile sorafenib administered at the maximum tolerated plasma AUC0-12h<br /><br>-To determine the skin and intratumoral concentrations of sorafenib and their correlation with the plasma and whole blood concentrations.<br /><br>-To select 1-2 optimal time points from the AUC0-12h data to determine sorafenib exposure in a high-dose, pulsatile schedule using a finger puncture.