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

• ClinicalTrials.gov Identifier: NCT03522649
• Recruitment Status: Unknown
• First Posted: May 11, 2018
• Last Update Posted: June 18, 2019
• Sponsor: 1Globe Health Institute LLC
• Information provided by (Responsible Party): 1Globe Biomedical Co., Ltd. ( 1Globe Health Institute LLC )

Tracking Information

• First Submitted Date: May 1, 2018
• First Posted Date: May 11, 2018
• Last Update Posted Date: June 18, 2019
• Actual Study Start Date: April 12, 2018
• Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 1, 2018)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 1, 2018)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase III Clinical Study of Napabucasin (GB201) Plus FOLFIRI 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
  Other Name: 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 Name: 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 Name: Irinotecan Aurobindo

Study Arms

• 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.
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 1, 2018): 668
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2021
• Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)

Eligibility 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/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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03522649
• Other Study ID Numbers: STEMNESS-CRC
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: 1Globe Biomedical Co., Ltd. ( 1Globe Health Institute LLC )
• Original Responsible Party: 1Globe Biomedical Co., Ltd.
• Current Study Sponsor: 1Globe Health Institute LLC
• Original Study Sponsor: 1Globe Biomedical Co., Ltd.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: 1Globe Biomedical Co., Ltd.
• Verification Date: May 2019