A phase I/II multicenter, open label study of TKI258 administered orally on an intermittent schedule in adult patients with advanced or metastatic Renal Cell Cancer (RCC)
- Conditions
- Renal cell carcinoma10038364
- Registration Number
- NL-OMON35681
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
Patients that must have been previously treated with sunitinib and/or sorafenib and mTor inhibitor. However, patients previously treated with other therapies (e.g. IL-2, IF-*) are also allowed to be enrolled and treated to determine the effect of TKI258 in patients who had not been treated with VEGF receptor tyrosine kinase inhibitor and mTOR therapy.
* Patients of Asian ethnicity: who failed standard treatment or for whom no standard therapy excists.
* Patients with at least one measurable lesion at baseline as per the RECIST.
* Serum creatinine * 1.5 x upper limit of normal (ULN)
* Absolute neutrophil count (ANC) * 1.5 x 109/L
* Platelets * 75 x 109/L
* Hemoglobin * 4.96 mmol/l
* Serum creatinine * 1.5 x upper limit of normal (ULN)
* Bilirubin * 1.5 x ULN
* AST (SGOT) and ALT (SGPT)* 2.5 x ULN, except for subjects with tumor
involvement of the liver who must have AST and ALT * 5 x ULN
* Amylase, Lipase * ULN
* Electrolyte levels should be within normal limits
* Urine dipstick: Negative for proteinuria or, if documentation of +1 results for protein on dipstick reading, then total urinary protein * 500 mg and measured creatinine clearance * 50 mL/min/1.73m2 from a 24-hour urine collection
* Clinically significant cardiac disease (New York Heart Association, Class III or IV) or impaired cardiac function or clinically significant cardiac diseases, including any one of the following: LVEF < 45%, Complete left bundle branch block, use of a cardiac pacemaker, Congenital long QT syndrome, History or presence of ventricular tachyarrhythmia, unstable atrial fibrillation, Clinically significant bradycardia, Hypertension * Grade 2, QTc > 480 msec, Right bundle branch block + left anterior hemiblock (bifasicular block), Angina pectoris * 3 months prior to starting study drug, Acute Myocardial Infarction * 3 months prior to starting study drug.
* Uncontrolled infection.
* Diabetes mellitus with signs of clinically significant peripheral vascular disease.
* Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month
* Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis,
adrenal or thyroid glands.
* Prior acute or chronic pancreatitis
* Acute and chronic liver disease and all chronic liver impairment.
* Malabsorption syndrome or uncontrolled gastrointestinal toxicities with toxicity >NCI CTCAE grade 2.
* Patients with brain metastases as assessed by radiologic imaging (e.g. CT, MRI)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the frequency of clinical responder and no clinical benefiter at 8<br /><br>weeks post-treatment. </p><br>
- Secondary Outcome Measures
Name Time Method <p>- To assess the safety profile of TKI258 administered orally on a 5 days on/2<br /><br>days off schedule in this patient population.<br /><br>- To characterize the single and multiple-dose pharmacokinetic (PK) profiles of<br /><br>oral TKI258 on a 5 days on/2 days off dosing schedule.<br /><br>- To assess the effect of TKI258 on plasma biomarkers pre- and post-treatment:<br /><br>* To evaluate concentrations of circulating growth factors, soluble receptors<br /><br>(e.g. bFGF, VEGF, PlGF, sVEGFR1 and 2).<br /><br>- To assess the relationship between dose and exposure of TKI258.<br /><br>- To explore the relationship between PK and biomarker responses (PD) of<br /><br>TKI258.</p><br>