First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib

An Uncontrolled, Open-label, Phase II Study in Subjects With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First Line Chemotherapy With mFOLFOX6 (Oxaliplatin/ Folinic Acid/5-fluorouracil [5-FU]) in Combination With Regorafenib

This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an oral (i.e. taken by mouth) multi-targeted kinase inhibitor. A kinase inhibitor targets certain key proteins that are essential for the survival of the cancer cell. By specifically targeting these proteins, regorafenib may stop cancer growth. The growth of the tumor may be decreased by preventing these specific proteins from functioning.

The primary endpoint (the most meaningful result to be tracked) of this study is based on the rate of response, i.e. the disease getting smaller. The aim is to show that the therapy of colorectal cancer with mFOLFOX6 in combination with regorafenib improves the response rate observed for the standard therapy only.

Inclusion Criteria:

• Male or female subjects aged ≥ 18 years
• Histological or cytological documentation of adenocarcinoma of the colon or rectum
• Suitable to receive mFOLFOX6 regimen as first line metastatic treatment
• At least 1 measurable lesion as per RECIST version 1.1
• Unresectable or unlikely becoming resectable metastatic disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of at least 3 months
• Adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Prior systemic anticancer therapy for metastatic colorectal cancer (CRC). Adjuvant chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended > 6 months before screening and recurrent disease was documented.
• Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any signal transduction inhibitors (STIs)
• Uncontrolled hypertension
• Subjects with symptoms, signs, or history of brain metastases
• Any hemorrhage or bleeding event ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks of start of study treatment
• Sensory neuropathy (> CTCAE Grade 1), unresolved toxicity > CTCAE Grade 1 attributed to any prior therapy/procedure excluding alopecia