Clinical Evaluation - A Phase IIA Proof of Concept Study of Regorafenib (Bayer 73-4506) in Biopsy-amenable Asian Colorectal Cancer Patients

Study Overview
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Brief Summary
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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) 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)

Official Title
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Clinical Evaluation - A Phase IIA Proof of Concept Study of Regorafenib (Bayer 73-4506) in Biopsy-amenable Asian Colorectal Cancer Patients

Conditions
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Asian Colorectal Cancer Patients

Intervention / Treatment
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* Drug: Regorafenib


Participation Criteria
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Eligibility Criteria
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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:

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Regorafenib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |