Title
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)
Phase
Phase 3Lead Sponsor
1Globe Biomedical Co., Ltd.Study Type
InterventionalStatus
Unknown statusIndication/Condition
Previously Treated Metastatic Colorectal CancerIntervention/Treatment
Napabucasin Fluorouracil Leucovorin IrinotecanStudy Participants
668This 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.
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours.
Fluorouracil 400 mg/m^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by Fluorouracil 1200 mg/m^2/day (total 2400 mg/m^2) continuous infusion.
Irinotecan 180 mg/m^2 followed by or concurrent with leucovorin 400 mg/m^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively.
Irinotecan 180 mg/m^2 followed by or concurrent with leucovorin 400 mg/m^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively.
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours. For patients who have failed bevacizumab with irinotecan-based chemotherapies, bevacizumab may be administered with FOLFIRI. FOLFIRI infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks, starting on C1D1. If bevacizumab is added to FOLFIRI, bevacizumab infusion should start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion. 5-FU 400 mg/ m^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/ m^2/day continuous infusion. For patients who could not tolerate FOLFIRI at the full dose previously, FOLFIRI should be started at the same dose level the patient tolerated FOLFIRI previously.
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours.
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
