Dose Escalation and Dose Expansion Study of GAS in Subjects With Metastatic Pancreatic Adenocarcinoma

NCT06229496 | Recruiting Phase 1 DMC

• 1 other identifier: 202300649A3
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 1b, open-label, multicenter, dose escalation and dose expansion study of S-1 in combination with nab-paclitaxel and gemcitabine (GAS) in subjects with metastatic pancreatic adenocarcinoma. This study is a dose escalation and dose expansion study with the objective to establish the MTD and/or RP2D and/or DLT of nab-paclitaxel and gemcitabine in combination with a body surface area(BSA)-based dose of S-1 in subject with metastatic pancreatic adenocarcinoma.

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

Dose escalation; Pancreatic adenocarcinoma; GAS

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  To determine a recommended Phase 2 dose (RP2D) of nab-paclitaxel and gemcitabine in combination with body surface area (BSA) - based dose of S-1 in subject with metastatic pancreatic adenocarcinoma

  From cycle 1 day 1 (each cycle is 14 days) untill the date of radiographic tumor assessment confirm tumor recurrence or specified AE occur, assessed up to 3 years

• Dose-limiting toxicity (DLT)

  From cycle 1 day 1 (each cycle is 14 days) untill the date of radiographic tumor assessment confirm tumor recurrence or specified AE occur, assessed up to 3 years

• Objective response rate (ORR)

  Tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.

  From cycle 1 day 1 (each cycle is 14 days) untill the date of radiographic tumor assessment confirm tumor recurrence or specified AE occur, assessed up to 3 years

Secondary Outcomes (5)

• Safety profile of GAS regimen

  From cycle 1 day 1 (each cycle is 14 days) untill the date of radiographic tumor assessment confirm tumor recurrence or specified AE occur, assessed up to 3 years

• Disease Control Rate (DCR)

  Through study completion, an average of 3 year

• Duration of Response (DoR)

  Through study completion, an average of 3 year

• Progression-free Survival (PFS)

  Through study completion, an average of 3 year

• Overall Survival (OS)

  Through study completion, an average of 3 year

Study Arms (3)

GAS regimen-dose level 1

EXPERIMENTAL

Combination Product: Gemcitabine 800mg/m2 + Nab-paclitaxel 100mg/m2 + S-1 (dose according to BSA)

GAS regimen-dose level 2

EXPERIMENTAL

Combination Product: Gemcitabine 800mg/m2 + Nab-paclitaxel 125mg/m2 + S-1 (dose according to BSA)

GAS regimen-dose level 3

EXPERIMENTAL

Combination Product: Gemcitabine 1000mg/m2 + Nab-paclitaxel 125mg/m2 + S-1 (dose according to BSA)

Interventions

Gemcitabine 800mg/m2 + Nab-paclitaxel 100mg/m2 + S-1 (dose according to BSA) COMBINATION_PRODUCT

Dose escalation study-dose level 1

GAS regimen-dose level 1

Gemcitabine 800mg/m2 + Nab-paclitaxel 125mg/m2 + S-1 (dose according to BSA) COMBINATION_PRODUCT

Dose escalation study-dose level 2

GAS regimen-dose level 2

Gemcitabine 1000mg/m2 + Nab-paclitaxel 125mg/m2 + S-1 (dose according to BSA) COMBINATION_PRODUCT

Dose escalation study-dose level 3

GAS regimen-dose level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed pancreatic adenocarcinoma (poorly differentiated carcinoma is allowed in the absence of neuroendocrine features or squamous differentiation)
• Treatment-naï ve stage IV disease (measurable disease is required). Prior adjuvant chemotherapy or radiochemotherapy is allowed, if completed ≥ 6 months before enrollment.
• Measurable disease defined as at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
• Life expectancy \> 6 months in the opinion of his/her treating physician.
• At least 18 years of age
• Ability to understand the nature of this study protocol, comply with study and/or follow-up procedures, and sign the IRB-approved written informed consent
• Fertile female and male patients with child-bearing potential agree to use adequate contraceptive measures prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥ 1500/uL Platelet count ≥ 100,000/uL Hemoglobin ≥ 9.0 g/dL
• Adequate hepatic function:
• Total bilirubin ≤ 1.5 X ULN (≤3.5 mg/dL if with adequate biliary tract drainage/stent placement) AST ≤ 3.0 X ULN (≤5.0X ULN if liver metastases are present) ALT ≤ 3.0 X ULN (≤5.0X ULN if liver metastases are present)
• Adequate renal function (defined as serum creatinine ≤ 1.5 X ULN or creatinine clearance rate (CCr) ≥ 50 mL/min (calculated by Cockroft-Gault formula; male: \[(140 - age in years) × weight in kg)\]/\[72 × serum creatinine(mg/dL)\];female=male x 0.85 )
• Able to take the oral study medication (S-1)
• No clinically significant abnormal ECG findings within 28 days (4 weeks) prior to enrollment

You may not qualify if:

• Have known endocrine pancreatic tumors or ampullary cancer
• Have received first line treatment for metastatic pancreatic cancer
• Have a serious concomitant active infection or other major comorbidities that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol (e.g., stroke, uncontrolled arrhythmia, heart failure, or active autoimmune disease)
• Have HIV history or hepatitis B and C infection, except for prescribing anti-hepatitis B medications for hepatitis B carrier and undetectable HCV RNA level for hepatitis C prior to enrollment.
• Have known central nervous system (CNS) malignancy or metastasis (screening is not required)
• Have concurrent hematologic malignancies, acute or chronic leukemia
• Have known additional malignancy that is progressing or required active treatments within the past 6 months, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast or cervical cancer)
• Women with a positive pregnancy test or who are breastfeeding
• Have participated within the last 30 days in a clinical trial involving an investigational product
• Unable to swallow capsules or has diseases significantly affecting gastrointestinal function or resection of the stomach or small bowel, malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• Current peripheral sensory neuropathy ≥ Grade 2
• Any social condition or diseases judged ineligible by physician for participation in the study due to safety concern

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (3)

Chiayi Chung Gung Memmorial Hospital

Chiayi City, 613, Taiwan

RECRUITING

Chang-Gung Memorial Hospital, Kaohsiung Branch

Kaohsiung City, Taiwan

NOT YET RECRUITING

Chang-Gung Memorial Hospital, Linkou Branch

Taoyuan, Taiwan

RECRUITING

MeSH Terms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; S 1 (combination)

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Wen-Kuan Huang, MD, PhD

CONTACT

03-3281200; medfox0924@cgmh.org.tw

Hao-Yun Hsiao, MD

CONTACT

03-3281200; hyhsiao@cgmh.org.tw

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 29, 2024
• Study Start: August 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

TW (3)