Investigating a new drug combination for advanced pancreatic cancer

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 testing a new combination of three drugs to see if it helps people with advanced pancreatic cancer feel better and live longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chang Gung Memorial Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 2 sites (Kaohsiung City and 1 other locations)
• Trial ID: NCT06229496 on ClinicalTrials.gov

What this trial studies

This Phase 1b, open-label, multicenter study evaluates the safety and efficacy of a new drug combination, S-1 with nab-paclitaxel and gemcitabine, in patients with metastatic pancreatic adenocarcinoma. The study aims to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of this combination therapy. Participants will receive varying doses of the drugs based on their body surface area, and the study will monitor their responses and any side effects. The goal is to explore whether this triplet combination can improve outcomes compared to existing treatments.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with treatment-naïve stage IV pancreatic adenocarcinoma and measurable disease.

Not a fit: Patients with non-measurable disease or those who have received prior chemotherapy within the last 6 months may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with advanced pancreatic cancer.

How similar studies have performed: While similar combinations have been explored, this specific triplet approach is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed pancreatic adenocarcinoma (poorly differentiated carcinoma is allowed in the absence of neuroendocrine features or squamous differentiation)
2. Treatment-naï ve stage IV disease (measurable disease is required). Prior adjuvant chemotherapy or radiochemotherapy is allowed, if completed ≥ 6 months before enrollment.
3. 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
4. Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
5. Life expectancy \> 6 months in the opinion of his/her treating physician.
6. At least 18 years of age
7. 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
8. 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.
9. Adequate bone marrow function:

   Absolute neutrophil count (ANC) ≥ 1500/uL Platelet count ≥ 100,000/uL Hemoglobin ≥ 9.0 g/dL
10. 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)
11. 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 )
12. Able to take the oral study medication (S-1)
13. No clinically significant abnormal ECG findings within 28 days (4 weeks) prior to enrollment

Exclusion Criteria:

1. Have known endocrine pancreatic tumors or ampullary cancer
2. Have received first line treatment for metastatic pancreatic cancer
3. 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)
4. 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.
5. Have known central nervous system (CNS) malignancy or metastasis (screening is not required)
6. Have concurrent hematologic malignancies, acute or chronic leukemia
7. 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)
8. Women with a positive pregnancy test or who are breastfeeding
9. Have participated within the last 30 days in a clinical trial involving an investigational product
10. 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.
11. Current peripheral sensory neuropathy ≥ Grade 2
12. Any social condition or diseases judged ineligible by physician for participation in the study due to safety concern

Where this trial is running

Kaohsiung City and 1 other locations

• Chang-Gung Memorial Hospital, Kaohsiung Branch — Kaohsiung City, Taiwan (Not_yet_recruiting)
• Chang-Gung Memorial Hospital, Linkou Branch — Taoyuan, Taiwan (Recruiting)

Study contacts

• Study coordinator: Wen-Kuan Huang, MD, PhD

Conditions Metastatic Pancreatic Adenocarcinoma; Dose escalation; Pancreatic adenocarcinoma; GAS