Advanced solid malignancies MedDRA version: 15.1 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Nexavar
Pharmaceutical Form:
INN or Proposed INN: SORAFENIB
CAS Number: 284461-73-0
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 800-
Trade Name: T
Sponsors
Medical Oncology, VUmc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must have a histologically confirmed diagnosis of an advanced or metastatic solid malignancy. • Patients must have confirmed radiological or clinical progressive disease. • Patients must have at least one measurable tumor lesion outside the liver. • Indication for standard use of palliative systemic treatment, with preference for standard treatment of sorafenib or erlotinib. • Age = 18 years. • ECOG Performance Status = 2. • Life expectancy of at least 12 weeks. • Patients should be able to swallow oral medication. • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: o Hemoglobin > 6.0 mmol/L o Absolute neutrophil count (ANC) >1,5 x 10*9/L o Platelet count ? 100 x 10*9/L o Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: • Concurrent treatment with other anticancer agents or experimental drugs. • History of cardiac disease: o Congestive heart failure >NYHA class 2. o Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening). • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). • Uncontrolled hypertension. Blood pressure must be =160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements. • Uncontrolled infections (> grade 2 NCI-CTC version 4.0). • Subjects with serious non-healing wound, ulcer, or bone fracture. • Patients with thromboembolic events within 3 months prior to study inclusion. • Significant skin condition interfering with treatment • Patients undergoing renal dialysis. • Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, or diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving the study kinase inhibitor. • Concomitant use of dexamethasone, anti-convulsants and anti-arrhythmic drugs other than digoxin or beta blockers. • Major surgery within 28 days prior to start of treatment. • Medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results. • Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to determine whether tumor concentrations of kinase inhibitors at pharmacological active doses can be predicted from PET studies using tracer amounts (microdosing) of corresponding radiolabeled kinase inhibitors. This objective includes the development and validation of pharmacokinetic models for radiolabeled kinase inhibitors as well as validation of the microdosing concept for kinase inhibitors. ;Secondary Objective: The secondary objectives include exploration whether kinase inhibitor kinetics depend on perfusion (as measured by [15O]water PET) or size (as measured by diagnostic CT/MRI) of tumor lesions and to investigate (in)activation of key pathways targeted by the specific kinase inhibitor. ;Primary end point(s): - Detection of [11C]sorafenib or [11C]erlotinib in tumor lesions before and during treatment with sorafenib and erlotinib, respectively. - Biodistribution of [11C]sorafenib or [11C]erlotinib before and during treatment with sorafenib and erlotinib, respectively. - Pharmacokinetics of [11C]sorafenib or [11C]erlotinib before and during treatment with sorafenib and erlotinib, respectively. - Tumorconcentrations of sorafenib or erlotinb after two weeks of treatment with sorafenib or erlotinib, respectively. ;Timepoint(s) of evaluation of this end point: Before start of treatment with sorafenib or erlotinib patients will be injected with [11C]sorafenib or [11C]erlotinib, resepctively. Immediately after injection a dynamic PET scan (microdosing) will be performed together with continuous arterial sampling. After two weeks of treatment with sorafenib or erlotinib patients will be injected a second time with [11C]sorafenib or [11C]erlotinib, resepctively. Immediately after injection a dynamic PET scan (therapeutic) will be performed together with continuous arterial sampling. Within two hours after the therapeutic scan a tumor biopsy will be performed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -phosphoproteomic analysis and (in)activation of key pathways invloved in sorafenib or erlotinib signaliing, resepectively. - measurement of perfusion of tumor lesions using [15O] water PET scan - size measurements of tumor lesions ;Timepoint(s) of evaluation of this end point: Immediately before the injection with [11C]sorafenib or [11C]erlotinib for the microdosing and the therapeutic PET scan, patients will be injected with [15O] water to perform a [15O]water PET scan. Within two hours after the microdosing scan (optional) and therapeutic scan a tumor biopsy will be taken. Tumor size will be measured on the diagnostic CT and/or MRI performed during screening. | — |
Countries
Netherlands
Contacts
Public ContactC.Willemien Menke
Medical Oncology, VUmc
Outcome results
None listed