A Study of GB201 in Combination With Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Pancreatic Cancer

A Phase II/III Randomized, Open-Label Clinical Study of GB201 in Combination With Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Metastatic Pancreatic Cancer Following Chemotherapy Failure

This is a Phase II/III Randomized, Open-Label Clinical Study of GB201 in Combination with Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Metastatic Pancreatic Cancer Following Chemotherapy Failure

INCLUSION CRITERIA

1. Written, signed consent for trial participation in accordance with applicable ICH guidelines.

2. Must have histologically or cytologically confirmed advanced pancreatic adenocarcinoma that is metastatic.

3. Patients who are candidates for and have access to gemcitabine-nab-paclitaxel or are candidates for FOLFIRINOX/mFOLFIRINOX must have received these standard of care regimens before randomization.

4. Must have one or more evaluable metastatic tumors by RECIST 1.1.

5. Must have ECOG Performance Status of 0 or 1.

6. Must have life-expectancy of > 12 weeks.

7. Must be ≥ 18 years of age.

8. For male or female patients of child producing potential: must agree to use contraception or take measures to avoid pregnancy.

9. Adequate biological parameters：

   • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
   • Platelet count ≥ 100,000/mm^3 (100 × 10^9/L).
   • Hemoglobin (Hgb) ≥ 9 g/dL.
   • AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) [5 ×ULN in presence of liver metastases]
   • Total bilirubin ≤ 1.5 × institutional ULN. If total bilirubin is > ULN, it must be non-rising for at least 3 days.
   • Serum creatinine within normal limits or calculated clearance > 60 mL/min/1.73 m^2.

10. Acceptable coagulation studies.

11. No clinically significant abnormalities on urinalysis.

12. Patient must have adequate nutritional status.

13. Pain symptoms should be stable (of tolerable Grade 2 or less).

14. Only patients with available archival tumor tissue must consent to submit block of tumor tissue.

15. The patient is not receiving therapy in a concurrent clinical study.

EXCLUSION CRITERIA

1. Anti-cancer chemotherapy, radiotherapy, biologic therapy or immunotherapy administered two weeks prior to the first planned dose of study medication. Investigational agents administered within four weeks of first planned dose of study medication.
2. Patients with any unresolved lingering toxicity > Grade 2 from prior treatment will be excluded.
3. Patient who were intolerant to prior taxane treatment.
4. Major surgery within 4 weeks prior to randomization.
5. Patients with any known brain or leptomeningeal metastases are excluded, even if treated.
6. Patients with clinically significant pleural effusion or ascites.
7. Patient with gastrointestinal disorder(s) which could significantly impede the absorption of an oral agent.
8. Prior treatment with napabucasin or participation in a clinical trial evaluating napabucasin.
9. Uncontrolled inter-current illness.
10. Known hypersensitivity to gemcitabine, taxanes or any of their excipients.
11. Uncontrolled chronic diarrhea ≥ grade 2 at baseline.
12. Patients being treated with any coumarins.
13. Patients with a history of other malignancies.