clinical evaluation - a phase iia proof of concept study of regorafenib (bayer 73-4506) in biopsy-amenable asian colorectal cancer patients

Conditions: Asian Colorectal Cancer Patients

Summary: 1. primary endpoints * biomarker data suggestive of regorafenib-mediated inhibition of the ras-raf- mek-erk signal transduction pathway,of various tyrosine kinase receptors and/or of angiogenesis. * evaluation of potential relationships between biomarker data and clinical activity. * evaluation of a novel biomarker technology (prometheus copia platform) 2. secondary endpoints * biomarker data suggestive of regorafenib-mediated effects on circulating rare cells. * comparison of tumor genetic profiles obtained using dna isolated from plasma, tumor biopsies and circulating tumor cells. * patient safety data * pharmacokinetics of regorafenib * changes in tumor metabolic activity as measured by pet ct scan (optional)


Eligibility criteria:
inclusion criteria: * histologically or cytologically proven metastatic colorectal adenocarcinoma that is refractory to standard therapy and not amenable to surgery with curative intent. * tumor characteristics: * at least one lesion that is suitable for a repeated biopsy; eg. subcutaneous nodule, skin lesion, rectal tumor, colonic mass easily reached by colonoscopy, peritoneal masses at least 3cm in maximum diameter that are easily assessable by image guided core biopsy. * for liver lesions, more superficially located lesions at least 3cm in maximum dimension with a rim of normal liver tissue, assessable safely by image guided core biopsy as determined by an experienced interventional radiologist. * eastern cooperative oncology group ecog performance status of 0 or 1 (see appendix 10.4). * adequate bone marrow function (absolute neutrophil count =1,500/mm3; platelet count =100000/mm3; hemoglobin =9g/dl * adequate liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment: * total bilirubin \< 1.5 x the upper limit of normal (uln). * alanine transaminase (alt) and aspartate aminotransferase (ast) \< 2.5 x uln (\< 5 x uln for patients with liver involvement of their cancer). * amylase and lipase \< 1.5 x the uln * serum creatinine \< 1.5 x the uln. * glomerular filtration rate (gfr) = 30 ml/min/1.73 m2 according to the mdrd (modified diet in renal disease) abbreviated formula * prothrombin time, international normalized ratio (inr) and partial thromboplastin time less than or equal to 1.2 times the uln. * male or female at least 21 years of age. * a female subject is eligible to enter and participate in the study if she is: * non-childbearing potential (ie. physiologically incapable of becoming pregnant) including any women who: * has had a hysterectomy or * has bilateral oophorectomy (ovariectomy) or * has bilateral tubal ligation or * is postmenopausal (demonstrate total cessation of menses for greater than or * childbearing potential, has a negative serum or urine pregnancy test at screening, agrees to one of the following: double barrier contraception or abstinence. * predicted life expectancy of at least 12 weeks. * resting oxygen saturation greater than 92% on room air. * written informed consent. * able to swallow and retain oral medication. * prothrombin time (pt), international normalized ratio for pt (pt inr), and partial thromboplastin time (ptt) or activated partial thromboplastin time (aptt) within normal limits. exclusion criteria: