Previously Treated Metastatic Colorectal Cancer
Conditions
Keywords
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.
Interventions
DRUGNapabucasin
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 8\ 12 hours.
DRUGFluorouracil
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.
DRUGLeucovorin
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.
DRUGIrinotecan
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.
Sponsors
1Globe Health Institute LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 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) | 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 | 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) | 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. |
| Progression free survival (PFS) | 43 months | Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. |
| Progression Free Survival in biomarker positive patients | 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 | 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 | 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. |
| Overall Survival in biomarker positive patients | 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. |
Countries
China
Contacts
Primary ContactLiu Wang
Outcome results
None listed