A Phase III Clinical Study of Napabucasin (GB201) Plus FOLFIRI in Adult Patients With Metastatic Colorectal Cancer
- Conditions
- Previously Treated Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT03522649
- Lead Sponsor
- 1Globe Health Institute LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 668
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Napabucasin plus FOLFIRI Fluorouracil 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 plus FOLFIRI Napabucasin 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 Napabucasin Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8\~12 hours. Napabucasin plus FOLFIRI Leucovorin 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 plus FOLFIRI Irinotecan 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 43 months To assess the effect of Napabucasin plus biweekly FOLFIRI versus Napabucasin on the Overall Survival of patients with previously treated metastatic colorectal cancer.
- Secondary Outcome Measures
Name Time Method Quality of Life (QoL) 43 months QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) in patients with pretreated metastatic CRC treated with Napabucasin plus biweekly FOLFIRI versus Napabucasin.
Number of Patients with Adverse Events 43 months All patients who have received at least one dose of Napabucasin will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.
Progression free survival (PFS) 43 months Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
Disease control rate (DCR) 43 months Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Objective Response Rate in biomarker positive patients 43 months Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1. This biomarker-positive sub-population is defined as those patients with nuclear β-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1. This biomarker-positive sub-population is defined as those patients with nuclear β-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.
Objective response rate (ORR) 43 months Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.
Overall Survival in biomarker positive patients 43 months To assess the effect of Napabucasin plus FOLFIRI versus Napabucasin on the Overall Survival of patients with metastatic colorectal cancer in biomarker positive patients. This biomarker-positive sub-population is defined as those patients with phospho-STAT3/nuclear β-catenin positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.
Progression Free Survival in biomarker positive patients 43 months Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. This biomarker-positive sub-population is defined as those patients with nuclear β-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.
Disease Control Rate in biomarker positive patients 43 months Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. This biomarker-positive sub-population is defined as those patients with nuclear β-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.
Trial Locations
- Locations (37)
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
The Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China
The Sixth Affiliated Hospital of Sun Yat - sen University
🇨🇳Guangzhou, Guangdong, China
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
The 81 Hospital of the Chinese People's Liberation Army
🇨🇳Nanjing, Jiangsu, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, Jiangsu, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Jiangsu Provence Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
The First Bethune Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Shanghai General Hospital
🇨🇳Shanghai, Shanghai, China
Liaoning Provincial Cancer Hospital
🇨🇳Shenyang, Liaoning, China
Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Ren Ji Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Xi' AnJiaotong University
🇨🇳Xi'an, Shanxi, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
The Second Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Sir Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Beijng Cancer Hospital
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Forth Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The Affiliated Hospital Qingdao University
🇨🇳Qingdao, Shandong, China
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China