A Study of Napabucasin in Combination With Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Pancreatic Cancer

Study Overview
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Brief Summary
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This is a Phase III Randomized, Open-Label Clinical Study of Napabucasin (GB201) in Combination with Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Metastatic Pancreatic Cancer Following Front-Line Chemotherapy Failure

Official Title
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A Phase III Randomized, Open-Label Clinical Study of Napabucasin (GB201) in Combination With Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Metastatic PANCreatic Cancer Following Front-Line Chemotherapy Failure

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: Napabucasin
* Drug: Paclitaxel
* Drug: Gemcitabine
* Other: Standard of care treatment options


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced pancreatic adenocarcinoma that is metastatic. Must have at least failed first line therapy Has one or more metastatic tumors evaluable by CT scan with contrast (or MRI, if patient is allergic to CT contrast media) per RECIST 1.1 Exclusion Criteria: Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of chemotherapy within period of time equivalent to the usual cycle length of the regimen Prior taxane therapy in the neoadjuvant or adjuvant setting with progression occurring within 6 months of completion of taxane therapy; or any taxane therapy in the locally advanced or metastatic setting. Patient has experienced a decline in ECOG performance status between baseline visit and within 3 days prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Napabucasin+Paclitaxel+Gemcitabine<br>Napabucasin will be administered twice daily, at 240 mg bid (480 mg total daily dose).Paclitaxel 80 mg/m^2 will be administered intravenously. Gemcitabine 600 mg/m^2 will be administered intravenously following paclitaxel infusion. This regimen will be repeated on Days 1, 8 and 15 of every 28-day cycle. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and have not demonstrated disease progression based on RECIST 1.1 criteria | Drug: Napabucasin<br>* Napabucasin will be administered twice daily, at 240 mg bid (480 mg total daily dose), one hour prior or two hours after meals<br>* Other names: GB201;Drug: Paclitaxel<br>* Paclitaxel 80 mg/m^2 will be administered on Days 1, 8 and 15 of every 28-day cycle<br>* Other names: Bendatax;Drug: Gemcitabine<br>* Gemcitabine 600 mg/m^2 will be administered intravenously following paclitaxel infusion on Days 1, 8 and 15 of every 28-day cycle<br>* Other names: Bendacitabin;|
| Active Comparator: Standard of care treatment options<br>Patients will receive standard of care treatment options treatment, including Fluorouracil and Leucovorin, Gemcitabine, Onivyde plus Fluorouracil and Leucovorin (if Onivyde has been approved to treat pancreatic cancer in the country/region), or best supportive care (BSC) alone, one of which will be assigned by the investigator for each patient. | Other: Standard of care treatment options<br>* Patient will receive standard of care treatment options, including Fluorouracil /Leucovorin, Gemcitabine, Onivyde plus Fluorouracil /Leucovorin (if Onivyde has been approved to treat pancreatic cancer in the country/region) or best supportive care (BSC) alone, one of which will be assigned by the investigator, per Investigator decision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The primary objective of this study is to compare overall survival (OS) of patients with metastatic pancreatic adenocarcinoma treated with Napabucasin in combination with weekly paclitaxel and Low-dose gemcitabine versus standard of care treatment options. | 30 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. | 30 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 | 30 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 | 30 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. The incidence of adverse events will be summarized by type of adverse event and severity. | 30 months | 
| Quality of Life (QoL) | European Organization for Research and Treatment of Cancer Quality of Life questionnaire（EORTC-QLQ-C30), is a self-administered cancer specific questionnaire with multi-dimensional scales. It consists of both multi-item scales and single item measures, including five functional domains, a global quality of life domain, three symptom domains, and six single items. For each domain or single item measure a linear transformation will be applied to standardize the raw score to range between 0 and 100. The endpoints in QoL analysis are the mean EORTC QLQ-C30 QoL change scores from baseline for the physical function and global health status/quality of life subscale scores. After transformation, higher scores in these two subscales mean better outcome | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic Cancer