Phase II, Open-label, Parallel 2-arm, Multi-center
Conditions
Keywords
Metastatic Pancreatic Cancer
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.
Interventions
Gemcitabine 800mg/m2 in N/S 250ml over 30 minutes (or fixed dose rate 10 mg/m2/min) IV infusion on day 1 repeated every 14 days.
DRUGNab paclitaxel
Nab-paclitaxel 125mg/m2 over 30 minutes IV infusion on day 1 repeated every 14 days, followed by Gemcitabine
DRUGS1
S-1 orally 60-100 mg/day day 1 to 7 on in a 2-week cycle. The dose of S-1 is defined as follows: * BSA \< 1.25 m2: 60 mg/day * 1.25 m2 ≤ BSA \< 1.5 m2: 80 mg/day * BSA ≥ 1.5 m2: 100 mg/day
DRUGleucovorin
leucovorin 30mg BID day 1 to 7 on in a 2-week cycle
DRUGOxaliplatin
Oxaliplatin 75mg/m2 in 250 mL of D5W over 120 minutes IV infusion on day 1 repeated every 14 days
Sponsors
National Health Research Institutes, Taiwan
China Medical University Hospital
National Cheng-Kung University Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Taichung Veterans General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best objective response rate (ORR) | 6 years | tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | 6 years | Defined as having complete response, partial response or stable disease at least 12 weeks. |
| Progression-free survival (PFS) | 6 years | from the start date of study treatment to the date of progression disease or death. |
| Overall survival (OS) | 6 years | from the start date of study treatment to the date of death. |
| Duration of response (DOR) | 6 years | time from documentation of tumor response to disease progression. |
| Incidence of Treatment-related Adverse Events [Safety and Tolerability] | 6 years | This study will utilize the NCI-CTCAE v5.0 for Adverse Event monitoring and reporting |
Countries
Taiwan
Contacts
STUDY_CHAIRLi-Tzong Chen, MD, Ph.D.
National Health Research Institutes, Taiwan
PRINCIPAL_INVESTIGATORYung-Yeh Su, M.D.
National Health Research Institutes, Taiwan
PRINCIPAL_INVESTIGATORShang-Hung Chen, M.D.
National Health Research Institutes, Taiwan
Outcome results
None listed