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History of Changes for Study: NCT03522649
A Phase III Clinical Study of Napabucasin (GB201) Plus FOLFIRI Versus Napabucasin in Adult Patients With Metastatic Colorectal Cancer
Latest version (submitted June 17, 2019) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 1, 2018 None (earliest Version on record)
2 May 10, 2018 Study Status and Study Identification
3 May 10, 2019 Arms and Interventions, Sponsor/Collaborators, Study Status, Contacts/Locations, Eligibility, Study Description and Study Identification
4 June 17, 2019 Recruitment Status, Study Status and Study Identification
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Study NCT03522649
Submitted Date:  May 1, 2018 (v1)
Open or close this module Study Identification
Unique Protocol ID: CRC468
Brief Title: A Phase III Clinical Study of Napabucasin (GB201) Plus FOLFIRI Versus Napabucasin in Adult Patients With Metastatic Colorectal Cancer
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2018
Overall Status: Recruiting
Study Start: April 12, 2018
Primary Completion: November 2021 [Anticipated]
Study Completion: November 2021 [Anticipated]
First Submitted: May 1, 2018
First Submitted that
Met QC Criteria:		 May 1, 2018
First Posted: May 11, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:		 May 1, 2018
Last Update Posted: May 11, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: 1Globe Biomedical Co., Ltd.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
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.
Detailed Description:
Open or close this module Conditions
Conditions: Previously Treated Metastatic Colorectal Cancer
Keywords: CRC
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 668 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Napabucasin plus FOLFIRI
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours (480 mg total daily dose). FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of Napabucasin and will be administered every 2 weeks. Irinotecan 180 mg/m^2 together with leucovorin 400 mg/m^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, at least 2 hours following the first daily dose of Napabucasin. 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. This regimen will be repeated on Day 1 of every 14 day cycle.
 Drug: Napabucasin
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose).
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 together 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 together with leucovorin 400 mg/m^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively.
Other Names:
  • Irinotecan Aurobindo
Napabucasin
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8~12 hours (480 mg total daily dose).
 Drug: Napabucasin
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose).
Other Names:
  • GB201
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Overall Survival (OS)
[ Time Frame: 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:
1. Progression free survival (PFS)
[ Time Frame: 43 months ]

Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
2. Objective response rate (ORR)
[ Time Frame: 43 months ]

Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.
3. Disease control rate (DCR)
[ Time Frame: 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.
4. Number of Patients with Adverse Events
[ Time Frame: 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.
5. Quality of Life (QoL)
[ Time Frame: 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.
6. Overall Survival in biomarker positive patients
[ Time Frame: 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.
7. Progression Free Survival in biomarker positive patients
[ Time Frame: 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.
8. Objective Response Rate in biomarker positive patients
[ Time Frame: 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.
9. Disease Control Rate in biomarker positive patients
[ Time Frame: 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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 TAS-102 must have received relevant 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
Open or close this module Contacts/Locations
Central Contact Person: Liu Wang
Telephone: +86-10-62336199
Email: wangliu@1globe-china.com
Locations: China, Guangdong
Sun Yat-sen University Cancer Center
[Recruiting]
Guangzhou, Guangdong, China, 510060
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:
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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services