Clinical trial NCT05026905: A Phase II Randomized Study of Gemcitabine and Nab-paclitaxel in Combination With S- 1/LV (GASL) or Oxaliplatin (GAP) as First-line Treatment for Metastatic Pancreatic Cancer
Official title: A Phase II Randomized Study of Gemcitabine and Nab-paclitaxel in Combination With S- 1/LV (GASL) or Oxaliplatin (GAP) as First-line Treatment for Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Phase II, Open-label, Parallel 2-arm, Multi-center
Keywords: Metastatic Pancreatic Cancer
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: China Medical University Hospital
name: National Cheng-Kung University Hospital
name: Kaohsiung Medical University Chung-Ho Memorial Hospital
name: Taichung Veterans General Hospital
First posted: 2021-08-30
Enrollment: 66
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Gemcitabine and nab-paclitaxel are one standard of care for metastatic pancreatic adenocarcinoma (mPDAC) but the progression free survival (PFS) of the regimen is only 5.5 months. Previous phase II study showed gemcitabine and nab-paclitaxel plus cisplatin had a PFS of 10.1 months in mPDAC. This study will evaluate the efficacy and safety of gemcitabine, nab-paclitaxel plus S-1/LV (GASL) against gemcitabine, nab-paclitaxel plus oxaliplatin (GAP) in patients with mPDAC.

Detailed description: Gemcitabine and nab-paclitaxel are one standard of care for metastatic pancreatic adenocarcinoma (mPDAC) but the progression free survival (PFS) of the regimen is only 5.5 months. Previous phase II study showed gemcitabine and nab-paclitaxel plus cisplatin had a PFS of 10.1 months in mPDAC. However, the nephrotoxicity of cisplatin is always a concern therefore cisplatin was substituted with oxaliplatin in current study. S-1 monotherapy has shown promising anti-tumor activity against PDAC with a manageable safety profile which provided the opportunity of combination with other agents. In this study, we will evaluate the efficacy and safety of gemcitabine, nab-paclitaxel plus S-1/LV (GASL) against gemcitabine, nab-paclitaxel plus oxaliplatin (GAP) in patients with mPDAC.

Eligibility criteria: Inclusion Criteria:

* A.Cytology or histology confirmed pancreatic adenocarcinoma with evidence of distant metastasis.Mixed component of other cell type (eg, adenosquamous, adenocarcinoma with neuroendocrine differentiation) is eligible but should notify PI before registration.
* B.No history of prior chemotherapy for pancreatic cancer, except adjuvant chemotherapy that completed at least 6 months before documentation of recurrence by imaging study.
* C.Patients with prior radiotherapy are eligible if there are other measurable target lesions that is not irradiated.
* D.At least one measurable lesion according to RECIST version 1.1
* E.Ability to understand and willingness to sign a written informed consent document.
* F.ECOG performance status 0-1
* G.Age of 20 years or above
* H.Adequate organ function as defined by the following criteria:

absolute neutrophil count (ANC) ≥ 1,500/mm3 hemoglobin level ≥ 9 g/dL platelet count ≥ 100,000/mm3 total bilirubin ≤ 2 ULN or ≤5 ULN if caused by biliary obstruction and achieving adequate drainage judged by investigator aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5.0×ULN in the presence of liver metastases creatinine clearance rate (CCr) ≥ 50 mL/min (24-hour urine collection or calculated by Cockroft-Gault formula; male: \[(140 - age) × weight (kg)\]/\[72 × serum creatinine(mg/dL)\];female=male x 0.85

-I.Patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study.

Exclusion Criteria:

* A. Other malignancy within the past 5 years except for adequately treated localized cancer or carcinoma in situ;All patients with other malignancy within the past 5 years should notify PI before registration.
* B.Active or uncontrolled infection;
* C.Significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications at physician discretion
* D.Pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential.
* E.History of active autoimmune disease within 3 years or use of steroid more than prednisolone 10mg/day.

Primary outcomes:
measure: Best objective response rate (ORR)
timeFrame: 6 years
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: 6 years
measure: Progression-free survival (PFS)
timeFrame: 6 years
measure: Overall survival (OS)
timeFrame: 6 years
measure: Duration of response (DOR)
timeFrame: 6 years
measure: Incidence of Treatment-related Adverse Events [Safety and Tolerability]
timeFrame: 6 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: National Health Research Institutes, Taiwan
name: Li-Tzong Chen, MD, Ph.D.
role: STUDY_CHAIR
affiliation: National Health Research Institutes, Taiwan
name: Yung-Yeh Su, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Health Research Institutes, Taiwan
name: Shang-Hung Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: