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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: GB201; Drug: Paclitaxel; Drug: Gemcitabine; Other: Standard of care treatment options

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Shirley Yuan; Phone Number: +86-15901044003; Email: yuanning@1globe-china.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provincial Cancer Hospital
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Chinese PLA General Hospital
    • Beijing, Beijing, China
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing, China
      • Recruiting
      • Beijng Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Medical University Union Hospital
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Provincial Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangdong General Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Xinxiang, Henan, China
      • Recruiting
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • People's Hospital of Hunan Province
    • Changsha, Hunan, China
      • Recruiting
      • The Third Xianya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • The 81 Hospital of the Chinese People Liberation Army
    • Nantong, Jiangsu, China
      • Recruiting
      • Nantong Tumor Hospital
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • The First Bethune Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China
      • Recruiting
      • The Second Hospital of Dalian Medical University
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China
      • Recruiting
      • Huashan Hospital Fudan University
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai General Hospital
    • Shanghai, Shanghai, China
      • Recruiting
      • East Hospital of Tongji University
    • Shanghai, Shanghai, China
      • Recruiting
      • Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China
      • Recruiting
      • Shanxi Provincial Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Medical University Cancer Institute Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Sir Run Shaw Hospital School of Medicine Zhejiang University
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital Zhejiang University
    • Jiaxing, Zhejiang, China
      • Recruiting
      • The First Hospital of Jiaxing
• France
  • Bourgogne, France
    • Recruiting
    • Institut de Cancérologie de Lorraine
  • Brest, France
    • Recruiting
    • Unité de Recherche Clinique en Cancérologie, Institut de cancérologie et d'hématologie
  • Nice, France
    • Recruiting
    • Centre Antoine Lacassagne
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebrón
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario HMN Sanchinarro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GB201+Paclitaxel+Gemcitabine; Patients randomized to Arm 1 will receive GB201 in combination with weekly paclitaxel and low-dose gemcitabine, with one treatment cycle defined as 4 weeks (28 days). GB201 will be administered orally, twice daily, with doses separated by approximately 8-12 hours. GB201 administration will begin 2-5 days prior to the first infusion of paclitaxel and low-dose gemcitabine. Paclitaxel and low-dose gemcitabine will be administered on Days 1, 8 and 15 of every 28-day cycle.	Drug: GB201; GB201 will be administered orally, twice daily, with doses separated by approximately 8-12 hours. GB201 administration will begin 2-5 days prior to the first infusion of paclitaxel and low-dose gemcitabine; Drug: Paclitaxel; Paclitaxel 80 mg/m^2 will be administered intravenously starting on Day 1 of Cycle 1. This regimen will be repeated on Days 1, 8 and 15 of every 28-day cycle; Drug: Gemcitabine; Low-dose gemcitabine 600 mg/m^2 will be administered intravenously following completion of paclitaxel infusion. This regimen will be repeated on Days 1, 8 and 15 of every 28-day cycle.
Active Comparator: Standard of care treatment options; Patients randomized to Arm 2 will receive one of the standard of care treatment options assigned by the Investigator for each patient prior to starting protocol treatment, including gemcitabine, capecitabine, 5-FU/LV, Onivyde plus 5- FU/LV (if Onivyde is available in the country/region) or best supportive care (BSC). Patients who have failed gemcitabine previously and were randomized to Arm 2 will not be eligible to receive gemcitabine as a treatment option.	Other: Standard of care treatment options; Patients will receive one of the standard of care treatment options assigned by the Investigator for each patient prior to starting protocol treatment, including Gemcitabine, capecitabine, 5-FU/LV, Onivyde plus 5-FU/LV (if Onivyde is available in the country/region) or best supportive care (BSC).; Other Names: BSC

What is the study measuring?

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 GB201 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
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
Safety by reporting the adverse events and serious adverse events	Assessment of safety of GB201 by reporting of adverse events and serious adverse events.	30 months

Collaborators and Investigators

• Sponsor: 1Globe Health Institute LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pancreatic Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Gemcitabine
• Other Study ID Numbers: STEMNESS-PANC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No