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.

Study Overview

• Status: Unknown
• Conditions: Previously Treated Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Napabucasin; Drug: Fluorouracil; Drug: Leucovorin; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Anticipated): 668
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • Recruiting
      • First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China, 230022
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230601
      • Recruiting
      • The Second Affiliated Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijng Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • The Sixth Affiliated Hospital of Sun Yat - sen University
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • Forth Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150040
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430023
      • Recruiting
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Not yet recruiting
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Jiangsu Cancer Hospital
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital
    • Nanjing, Jiangsu, China, 210002
      • Recruiting
      • The 81 Hospital of the Chinese People's Liberation Army
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Provence Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Bethune Hospital of Jilin University
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Recruiting
      • Liaoning Provincial Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
    • Qingdao, Shandong, China, 266103
      • Recruiting
      • The Affiliated Hospital Qingdao University
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Recruiting
      • Shanghai East Hospital
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital
    • Shanghai, Shanghai, China, 200092
      • Recruiting
      • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Ren Ji Hospital, Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi' AnJiaotong University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310006
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • The Second Affiliated Hospital, Zhejiang University
    • Hangzhou, Zhejiang, China, 310016
      • Recruiting
      • Sir Run Shaw Hospital, school of medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Napabucasin plus FOLFIRI; 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.	Drug: Napabucasin; Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours.; Other Names: GB201; Drug: 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.; Other Names: 5-FU; Benda-5 FU; Drug: 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.; Other Names: Folinic Acid; Drug: 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.; Other Names: Irinotecan Aurobindo
Other: Napabucasin; Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours.	Drug: Napabucasin; Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours.; Other Names: GB201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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 β-catenin positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months
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 β-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months
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 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.	43 months
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 β-catenin and/or phospho-STAT3 positivity on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) archival tissue.	43 months

Collaborators and Investigators

• Sponsor: 1Globe Health Institute LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2018
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: June 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: CRC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan
• Other Study ID Numbers: STEMNESS-CRC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No