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

• ClinicalTrials.gov Identifier: NCT03721744
• Recruitment Status: Recruiting
• First Posted: October 26, 2018
• Last Update Posted: April 3, 2024
• Sponsor: 1Globe Health Institute LLC
• Information provided by (Responsible Party): 1Globe Biomedical Co., Ltd. ( 1Globe Health Institute LLC )

Tracking Information

• First Submitted Date: October 25, 2018
• First Posted Date: October 26, 2018
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: October 25, 2018
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2024)

Overall survival (OS) [ Time Frame: 30 months ]

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.

Original Primary Outcome Measures (submitted: October 25, 2018)

Overall survival (OS) [ Time Frame: 30 months ]

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.

Current Secondary Outcome Measures (submitted: April 1, 2024)

• Progression free survival (PFS) [ Time Frame: 30 months ]
  Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
• Objective response rate (ORR) [ Time Frame: 30 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) [ Time Frame: 30 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
• Quality of Life (QoL) [ Time Frame: 30 months ]
  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
• Safety by reporting the adverse events and serious adverse events [ Time Frame: 30 months ]
  Assessment of safety of GB201 by reporting of adverse events and serious adverse events.

Original Secondary Outcome Measures (submitted: October 25, 2018)

• PFS [ Time Frame: 30 months ]
  Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
• ORR [ Time Frame: 30 months ]
  Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1
• DCR [ Time Frame: 30 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 [ Time Frame: 30 months ]
  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.
• Quality of Life (QoL) [ Time Frame: 30 months ]
  QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of GB201 in Combination With Weekly Paclitaxel and Low-dose Gemcitabine in Patients With Pancreatic Cancer
• Official Title: 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
• Brief Summary: 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Pancreatic Cancer

Intervention

• 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.
• 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 Name: BSC

Study Arms

• 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.

  Interventions:

  • Drug: GB201
  • Drug: Paclitaxel
  • Drug: Gemcitabine
• 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.
  Intervention: Other: Standard of care treatment options

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 1, 2024): 336
• Original Estimated Enrollment (submitted: October 25, 2018): 230
• Estimated Study Completion Date: September 2025
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Shirley Yuan; +86-15901044003; yuanning@1globe-china.com

• Listed Location Countries: China, France, Spain

Administrative Information

• NCT Number: NCT03721744
• Other Study ID Numbers: STEMNESS-PANC
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: 1Globe Biomedical Co., Ltd. ( 1Globe Health Institute LLC )
• Original Responsible Party: 1Globe Biomedical Co., Ltd.
• Current Study Sponsor: 1Globe Health Institute LLC
• Original Study Sponsor: 1Globe Biomedical Co., Ltd.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: 1Globe Biomedical Co., Ltd.
• Verification Date: April 2024