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

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Treatments: Niclosamide

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: