se of individual PK-guided pazopanib dosing: A feasibility study in patients with advanced solid tumors

Recruiting

Conditions: cancer
malignancy
10027655

Registration Number: NL-OMON40372

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

1) Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
Note: Procedures conducted as part of the subject*s routine clinical management (e.g., blood count, imaging study such as bone scan) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
2) Age >= 18 years
3) Histopathologically confirmed advanced tumors for which pazopanib is considered standard of care or patients with advanced or metastatic tumors for whom no standard therapy is available;
4) Eastern Cooperative Oncology Group (ECOG) or WHO performance status of 0-1
5) Evaluable disease according to RECIST 1.1 criteria
6) Adequate organ system function as defined in Table 3
Table 3: Definitions for Adequate Organ Function
System Laboratory Values
Hematology
Absolute neutrophil count (ANC) *1.5 X 109/L
Hemoglobina
*5.6 mmol/L
Platelets *100 X 109/L
Prothrombin time (PT) or international normalized ratio (INR)a *1.2 X ULN
Activated partial thromboplastin time (aPTT) *1.2 X ULN
Hepatic
Total bilirubin *1.5 X ULN
Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)b *2.5 X ULN
Renal
Serum creatinine *133 µmol/L
Or, if >133 µmol/L : Calculated creatinine clearance (ClCR) *30 mL/min to *50 mL/min
Urine Protein (disptick) <2+
Or, 24-hour urine protein <1g
a. Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.
b. Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted.;7) Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception during the study and for 14 days following the last dose of investigational product.

Exclusion Criteria

1. Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 4 week interval.
2. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding
3. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
4. Corrected QT interval (QTc) > 480 msecs
5. 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)
6. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by the Principle Investigator in order for a subject to be eligible for the study.
7. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
8. Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
9. Evidence of active bleeding or bleeding diathesis.
10. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
11. Recent hemoptysis (** teaspoon of red blood within 8 weeks before first dose of study drug).
12. 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.
13. Unable or unwilling to discontinue use of prohibited medications in for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study (Chapter 8.7).
14. Treatment with any of the following anti-cancer therapies:
• radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
• 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
15. Administration o