Optimizing Pazopanib Exposure in RCC Patients

Inclusion Criteria:

* signature of informed consent
* age ≥ 18 years
* histologically confirmed renal cell carcinoma with clear cell component and either locally progressed or metastasized
* ECOG ≤ 2
* No previous systemic therapy for locally progressed or metastasized renal cell carcinoma (previous adjuvant or neo-adjuvant therapy is permitted)
* Adequate organ function
* Female patients with child-bearing potential with negative serum pregnancy test within 2 weeks prior to first dose of study medication and adequate contraception
* Lactating females

Exclusion Criteria:

* Clinically suspected and known metastases of the central nervous system or carcinomatous meningitis except in asymptomatic patients with previously treated CNS-metastases and no necessity of steroids or anti-epileptic medication ≥ 6 months prior to start of the study medication
* Clinically significant gastrointestinal conditions with risk of increase of gastrointestinal bleeding due to (but not limited to)
* active peptic ulceration
* known intraluminal metastases with risk of bleeding
* chronic-inflammatory intestinal disease (like Morbus Crohn, ulcerative colitis) or another gastrointestinal disease with increased risk of perforation
* abdominal fistulas in anamnesis
* Clinically significant gastrointestinal conditions which can influence absorption of the IMP, among others (but not limited to)
* malabsorption syndrome
* resection of stomach or small bowel
* Current uncontrolled infection
* QTc corrected for heart frequency according to the Bazett formula
* One or more of the following cardiovascular diseases within the last 6 months in the anamnesis:
* cardiac angioplasty or coronary stent implantation
* myocardial infarction
* instable angina pectoris
* coronary-arterial bypass surgery
* symptomatic peripheral arterial occlusive disease
* Heart failure NYHA III or IV
* Poorly controlled high blood pressure
* Cerebrovascular disease, including transitory ischemic attacks, pulmonary artery embolism or untreated deep vein thrombosis within 6 months of study inclusion
* Previous major surgery or traumas within 28 days prior to start if study treatment or non-healing wound, fracture or ulcer
* Clinical signs of active bleeding or bleeding diathesis
* Known endobronchial lesions or lesions infiltrating the large lung arteries
* Haemoptyses of \> 2.5 mL within 8 weeks prior to first intake of study medication
* Any other severe and/or instable medical or psychiatric pre-existing or other condition influencing patient safety, consent capacity or compliance within the study
* Incapacity or rejection to stop not allowed medication prior to first intake of study drug and pause for the duration of the trial
* Treatment with one of the following anti-tumour therapies:
* Radiation or tumour embolism within 14 days before first intake of study drug
* Chemotherapy, Immunotherapy, biological therapy, study medication or hormonal therapy within 14 days or 5 half-lives of the respective substance (whichever is longer) before first intake of the study drug. Neo-adjuvant or adjuvant therapy must have been completed for at least 6 months.
* Any present toxicity \> CTC 1° from prior anti-tumour therapy and/or toxicities worsening in severity except alopecia