Therapeutic Drug Monitoring to Individualize the Dosing of pazopanib: a Randomized Pharmacokinetic Feasibility Study
- Conditions
- advanced tumors for which no treatment options are availablerenal cell cancer10038588
- Registration Number
- NL-OMON37356
- Lead Sponsor
- eids Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 13
- Age * 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- No radio-, chemo- or tumorspecific targeted therapy within the last 4 weeks prior to study entry
- Adequate organ system function
- Patients or partners of patients with childbearing potential should practice adequate contraception (double barrier protection).
- Patient who are lactating should discontinue nursing prior to the first dose and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
- Current treatment in another therapeutic clinical trial
- History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
- Presence of uncontrolled infection.
- Corrected QT interval (QTc) > 480 msecs using Bazett*s formula (QTc = QT/*RR)
- History of any one or more of the following cardiovascular conditions within the past 6 months:
* Cardiac angioplasty or stenting
* Myocardial infarction
* Unstable angina
* Coronary artery bypass graft surgery
* Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of *140 mmHg or diastolic blood pressure (DBP) of * 90mmHg].
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
- Hemoptysis in excess of 2.5 mL (or one half teaspoon) in the last 8 weeks
- Increased risk of haemorrhage (treated with coumarines or low molecular weight heparine).
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject*s safety, provision of informed consent, or compliance to study procedures.
- Unable or unwilling to discontinue use of prohibited medications listed in appendix B for at least 14 days or five half lives of a drugs (whichever is longer) prior to the first dose of study drug and for the duration of the study
- Concurrent use of other substances known or likely to interfere with the pharmacokinetics of pazopanib (http://medicine.iupui.edu/clinpharm/ddis/)
- Treatment with any of the following anti-cancer therapies:
a. radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
b. chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>By introducing PK-guided dosing we hypothesize that the interpatient<br /><br>variability can be reduced by 50%. In this relatively small feasibility study<br /><br>we collect the evidence that PK-guided dosing in the future can be applied to<br /><br>increase efficacy and reduce toxicity by targeting the right exposure levels of<br /><br>pazopanib.</p><br>
- Secondary Outcome Measures
Name Time Method