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

Previously Treated Metastatic Colorectal Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03522649
• Other study ID #: STEMNESS-CRC
• Status: Recruiting
• Phase: Phase 3
• Start date: April 12, 2018
• Est. completion date: November 2021

Study information

• Verified date: May 2019
• Source: 1Globe Biomedical Co., Ltd.
• Contact: Liu Wang
• Phone: +86-10-62336199
• Email: wangliu[@]1globe-china.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 668
• Est. completion date: November 2021
• Est. primary completion date: November 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Previously Treated Metastatic Colorectal Cancer

Intervention

Drug:
• Napabucasin
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours.
• Fluorouracil
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.
• Leucovorin
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
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.

Locations

Country	Name	City	State
China	Beijng Cancer Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat - sen University	Guangzhou	Guangdong
China	Sir Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	The Second Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Shandong Cancer Hospital	Jinan	Shandong
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Jiangsu Provence Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	The 81 Hospital of the Chinese People's Liberation Army	Nanjing	Jiangsu
China	The Affiliated Hospital Qingdao University	Qingdao	Shandong
China	Ren Ji Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Liaoning Provincial Cancer Hospital	Shenyang	Liaoning
China	Forth Hospital of Hebei Medical University	Shijiazhuang	Hebei
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	The First Affiliated Hospital of Xi' AnJiaotong University	Xi'an	Shanxi
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
1Globe Health Institute LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	To assess the effect of Napabucasin plus biweekly FOLFIRI versus Napabucasin on the Overall Survival of patients with previously treated metastatic colorectal cancer.	43 months
Secondary	Progression free survival (PFS)	Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.	43 months
Secondary	Objective response rate (ORR)	Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.	43 months
Secondary	Disease control rate (DCR)	Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.	43 months
Secondary	Number of Patients with Adverse Events	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.	43 months
Secondary	Quality of Life (QoL)	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.	43 months
Secondary	Overall Survival in biomarker positive patients	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 ß-catenin positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months
Secondary	Progression Free Survival in biomarker positive patients	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 ß-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months
Secondary	Objective Response Rate in biomarker positive patients	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 ß-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 ß-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months
Secondary	Disease Control Rate in biomarker positive patients	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 ß-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months