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 Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Phase II, Open-label, Parallel 2-arm, Multi-center

Intervention / Treatment
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* Drug: Gemcitabine 1000 mg
* Drug: Nab paclitaxel
* Drug: S1
* Drug: leucovorin
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: GASL arm<br>eligible patients will receive gemcitabine 800 mg/m2 on day 1, nab-paclitaxel 125 mg/m2 on day 1, S-1 orally 60-100 mg/day [depending on patient's baseline body surface area (BSA)] on day 1 to 7 and leucovorin 30mg BID 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 | Drug: Gemcitabine 1000 mg<br>* 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.<br>* Other names: Gemcitabine;Drug: Nab paclitaxel<br>* Nab-paclitaxel 125mg/m2 over 30 minutes IV infusion on day 1 repeated every 14 days, followed by Gemcitabine<br>* Other names: nab-paclitaxel;Drug: S1<br>* 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<br>* Other names: S-1;Drug: leucovorin<br>* leucovorin 30mg BID day 1 to 7 on in a 2-week cycle<br>* Other names: Calcium Folinate tablet;|
| Other: GAP arm<br>eligible patients will receive gemcitabine 800 mg/m2, nab-paclitaxel 125 mg/m2 and oxaliplatin 75mg/m2 on day 1 in a 2-week cycle. | Drug: Gemcitabine 1000 mg<br>* 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.<br>* Other names: Gemcitabine;Drug: Nab paclitaxel<br>* Nab-paclitaxel 125mg/m2 over 30 minutes IV infusion on day 1 repeated every 14 days, followed by Gemcitabine<br>* Other names: nab-paclitaxel;Drug: Oxaliplatin<br>* Oxaliplatin 75mg/m2 in 250 mL of D5W over 120 minutes IV infusion on day 1 repeated every 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best objective response rate (ORR) | tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1. | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | Defined as having complete response, partial response or stable disease at least 12 weeks. | 6 years | 
| Progression-free survival (PFS) | from the start date of study treatment to the date of progression disease or death. | 6 years | 
| Overall survival (OS) | from the start date of study treatment to the date of death. | 6 years | 
| Duration of response (DOR) | time from documentation of tumor response to disease progression. | 6 years | 
| Incidence of Treatment-related Adverse Events [Safety and Tolerability] | This study will utilize the NCI-CTCAE v5.0 for Adverse Event monitoring and reporting | 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Pancreatic Cancer