First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Regorafenib (Stivarga, BAY73-4506); Oxaliplatin; Folinic acid; 5-FU (mFOLFOX6)
Intervention description: Subjects will receive regorafenib 160 mg od on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets. In case of administration as a single agent during the study, regorafenib will be administered 160 mg od for 3 weeks on/1 week off. Each cycle consists of 28 days.; On day 1 and day 15 of each cycle, participants will receive 85 mg/m^2 oxaliplatin as a 2 hour i.v. infusion.; On day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m^2 D/L-folinic acid or 200 mg/m^2 L-folinic acid) as a 2 hour i.v. infusion.; Participants will receive a 400 mg/m^2 5 FU i.v. bolus injection immediately followed by a 2400 mg/m^2 5 FU 46 hour i.v. infusion.
Intervention MeSH terms: Leucovorin; Folic Acid; Oxaliplatin; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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