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

NCT ID: NCT01189903

Last Updated: 2014-01-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31

Brief 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)

Conditions

Asian Colorectal Cancer Patients

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Regorafenib

Intervention Type: DRUG

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Principal Investigators

Boon Cher Goh, MBBS, MRCP

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

National University Hospital

Singapore, Singapore, Singapore

Countries

Singapore

References

Goh BC, Fleming GF, Janisch L, Vogelzang NJ, Stadler WM, Ratain MJ. Development of a schedule-dependent population pharmacodynamic model for rhizoxin without quantitation of plasma concentrations. Cancer Chemother Pharmacol. 2000;45(6):489-94. doi: 10.1007/s002800051024.

Reference Type: BACKGROUND

PMID: 10854137 (View on PubMed)

Vokes EE, Goh BC, Bertucci D, Vogelzang NJ, Mani S, Ratain MJ. A Phase I study of raltitrexed and paclitaxel given every 3 weeks to patients with solid tumors. Cancer. 1999 Aug 1;86(3):528-32.

Reference Type: BACKGROUND

PMID: 10430263 (View on PubMed)

Other Identifiers

CR01/18/10

Identifier Type: -

Identifier Source: org_study_id