Optimizing Pazopanib Exposure in RCC Patients
Optimizing Pazopanib Exposure in RCC Patients Through Therapeutic Drug Monitoring Followed by Intrapatient Dose Escalation
  • Phase

    Phase 2
  • Study Type

  • Status

  • Intervention/Treatment

    pazopanib ...
  • Study Participants

Optimization of Pazopanib Exposition in Patients with Renal Cell Carcinoma by Therapeutic Drug Monitoring followed by Individual Dose Escalation.
This is an open, multi-center, intraindividual dose-optimization study. Patients with locally advanced or metastatic renal cell carcinoma receive 800 mg Pazopanib daily. After 14 days the Pazopanib plasma concentration is determined. In patients who show good tolerability and plasma trough levels of ≤ 20 µg/mLthe daily dose is increased in 200 mg steps until plasma trough levels of > 20 µg/mL are achieved or dose-limiting toxicities occur, a daily dose of 1600 mg is reached, or there is disease progression.

After each dose optimization the plasma concentration is determined after 14 days (day 11-15). If indicated, dose optimization is performed 21 days after the previous dose optimization (on day 18-24).
Study Started
Feb 25
Primary Completion
Mar 22
Study Completion
Mar 22
Last Update
Aug 18

Drug Pazopanib

Normal plasma level patients and low plasma level patients. Experimental

Patients with normal Pazopanib plasma trough levels; "normal plasma level patients" (NPLP). Patients with low Pazopanib plasma trough levels, "low plasma level patients" (LPLP).


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
No Results Posted