Measurement of tumor kinase inhibitor concentrations using PET imaging in patients with advanced solid malignancies

Completed

Conditions: advanced cancer
metastasized malignancy
10027655

Registration Number: NL-OMON40107

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

* Patients must have a histologically confirmed diagnosis of an advanced or metastatic solid malignancy. ;* A. Patients must have confirmed radiological or clinical progressive disease with a standard indication to start sorafenib or erlotinib (category 1).
OR B. Patients must have stable disease for at least 4 months, a partial response or a complete response established with RECIST version 1.1 within 21 days before the radiolabeled kinase inhibitor scan if they are already on treatment with sorafenib or erlotinib (category 2).;* Patients must have at least one measurable tumor lesion outside the liver.;* Indication for standard use of palliative systemic treatment, with 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 * 2 times the upper limit of normal (ULN);o ALT and AST* 2.5 x ULN; * 5x ULN in case of liver metastases, except for patients with hepatocellular carcinoma, than Child Pugh classification A-B.;o Alkaline phosphatase < 4 x ULN; * 5x ULN in case of liver metastases, except for patients with hepatocellular carcinoma, than Child Pugh classification A-B.;o Serum creatinine eGFR * 50 mL/min. ;o PT-INR/PTT < 1.5 x ULN, unless coumarin derivatives are used.;o Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed, if this treatment can be interrupted for a biopsy as judged by the treating physician).

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1) Tumor uptake of [11C]sorafenib cq [11C]erlotinib before and on treatment (%<br /><br>injected dose and activity concentration in tumor lesions)<br /><br>2) Image derived imput function of [11C]sorafenib cq [11C]erlotinib before and<br /><br>on treatment (% injected dose and activity concentration in large bloodvessels)<br /><br>3) Pharmacokinetics [11C]sorafenib cq [11C]erlotinib before and on treatment<br /><br>(plasma and whole blood; % injected dose and activity concentration/g)<br /><br>4)On treatment tumor concentration of sorafenib cq erlotinib.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>5) Tumor perfusion as measured with [15O]water before and on treatment (%<br /><br>injected dose and activity concentration in tumor lesions)<br /><br>6) Image derived imput function of [15O]water before and on treatment (%<br /><br>injected dose and activity concentration in large bloodvessels)<br /><br>7) Kinase activity in tumor biopsies before and after treatment with sorafenib<br /><br>cq erlotinib.<br /><br>8) Phosphoproteomics analysisin tumor biopsies before and after treatment with<br /><br>sorafenib cq erlotinib.</p><br>