A Phase III Clinical Study of Napabucasin (GB201) Plus FOLFIRI in Adult Patients With Metastatic Colorectal Cancer

A Phase III, Randomized, Open-Label Clinical Study of Napabucasin (GB201) in Combination With FOLFIRI Versus Napabucasin in Adult Patients With Previously Treated Metastatic Colorectal Cancer (CRC)

This is a randomized, open-label, multi-center, phase III study of Napabucasin plus bi-weekly FOLFIRI (Arm 1) vs. Napabucasin (Arm 2) for adult patients with metastatic CRC who have failed standard chemotherapy regimens. For patients who have failed bevacizumab with irinotecan-based chemotherapies (treatment failure is defined as radiologic progression of disease during or within 3 months following the last dose), bevacizumab maybe administered in combination with FOLFIRI to patients randomized to Arm 1.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the colon or rectum that is metastatic (Stage IV)
• Progression during or within 3 months following the last administration of standard chemotherapy based regimens containing a fluoropyrimidine, irinotecan and oxaliplatin. Patients treated with oxaliplatin or irinotecan in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
• Patients who are candidates for and have access to anti-VEGF therapy (i.e. bevacizumab and regorafenib) and anti-EGFR therapy (i.e. cetuximab and panitumumab) and/or TAS-102 must have received appropriate therapy.
• Patients with measurable or non measurable disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status of </= 1
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Anti-cancer chemotherapy, biologic therapy or any other systemic therapy if administered prior to the first planned dose of study medication within period of time equivalent to the usual cycle length of the regimen. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of protocol treatment.
• Major surgery within 4 weeks prior to randomization.
• Any known brain or leptomeningeal metastases are excluded, even if treated.
• Known hypersensitivity to 5-FU/LV or patients who as a result of toxicity had to reduce or stop 5-FU infusion at the dose of 900 mg/m^2/day (total 1800 mg/m^2/day).
• Known hypersensitivity to irinotecan or patients who as a result of toxicity had to reduce or stop irinotecan infusion at the dose of 120 mg/m^2.
• Known history of human immunodeficiency virus (HIV) infection. Known chronic hepatitis B or C active infection.
• Known microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Patients with QTc interval > 470 millisecond.
• Uncontrolled intercurrent illness