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

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

Condition or disease Intervention/treatment Phase
Previously Treated Metastatic Colorectal Cancer Drug: Napabucasin Drug: Fluorouracil Drug: Leucovorin Drug: Irinotecan Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 668 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 12, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


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 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

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 Name: GB201




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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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/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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03522649


Contacts
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Contact: Liu Wang +86-10-62336199 wangliu@1globe-china.com

  Show 37 Study Locations
Sponsors and Collaborators
1Globe Health Institute LLC

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Responsible Party: 1Globe Health Institute LLC
ClinicalTrials.gov Identifier: NCT03522649     History of Changes
Other Study ID Numbers: STEMNESS-CRC
First Posted: May 11, 2018    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: May 2019

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

Keywords provided by 1Globe Biomedical Co., Ltd. ( 1Globe Health Institute LLC ):
CRC

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Fluorouracil
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs