Nab-paclitaxel Plus S-1(AS) Versus Nab-paclitaxel Plus Gemcitabine(AG) in Patients With Advanced Pancreatic Cancer

Phase 2

• Conditions: Pancreatic Cancer
• Interventions: Drug: nanoparticle albumin-bound paclitaxel; Drug: S1; Drug: Gemcitabine

• Registration Number: NCT03636308
• Lead Sponsor: Peking University

Brief Summary

This is a randomized phase II trial comparing the first-line treatment with nab-paclitaxel plus S-1(AS) and nab-paclitaxel plus gemcitabine(AG) in advanced pancreatic ductal adenocarcinoma (PDA) with primary tumor nonexcision in Chinese patients.

Detailed Description

Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemo-resistant disease with extremely low 5-year survival rate. Gemcitabine has been the cornerstone of metastatic PDAC treatment for more than a decade , although survival benefit was very poor. Nab-paclitaxel added to gemcitabine has showed improving survival and overall response rate vs gemcitabine alone in metastatic PDAC first-line treatment in the MPACT phaseIII study, which represents one of the standards of care in advanced PDAC therapy. S-1 is an oral 5-fluorouracil (5-FU) prodrug, and shown to be non-inferior to gemcitabine on OS for unresectable pancreatic cancer. Meanwhile, adjuvant chemotherapy with S-1 monotherapy was found to significant prolong survival of pancreatic cancer patients when compared with gemcitabine. This study is to explore the efficacy and safety of nab-paclitaxel plus S-1(AS) and nab-paclitaxel plus gemcitabine(AG) as first-line treatment in advanced pancreatic ductal adenocarcinoma (PDA) with primary tumor nonexcision in Chinese patients.

Study Timeline

• Study Start: 2018-07-17
• Status Verified: 2018-08
• Study First Submitted: 2018-08-01
• Study First Submitted QC: 2018-08-15
• Last Update Submitted: 2018-08-15
• Study First Posted: 2018-08-17
• Last Update Posted: 2018-08-17
• Primary Completion: 2020-08-01
• Study Completion: 2021-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Signed informed-consent form.
2. Age no less than 18 years.
3. Histologically confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma, with RECIST measurable lesions.
4. Eastern Cooperative Oncology Group (ECOG) 0-1 with life expectation of no less than 12 weeks.
5. Patients must have received no previous chemotherapy or investigational therapy for the treatment of locally advanced or metastatic disease.
6. At least 4 weeks since completion of the last operation except for diagnostic biopsy.
7. At least 4 weeks since completion of radiotherapy to lesions.
8. Not suitable for local treatment.
9. Adequate liver/bone marrow function.
10. Human Chorionic Gonadotropin (HCG) test negative for female with contraception measure until 3 months after study end.
11. Compliant, and can be followed up regularly.

Exclusion Criteria

1. Received chemotherapy or investigational therapy for the treatment of locally advanced or metastatic disease.
2. Pregnant or breast-feeding female, or not willing to take contraception measures during study.
3. Serious infection requiring antibiotics intervention during recruitment.
4. Allergic to study drug.
5. More than grade 1 neuropathy.
6. Uncontrolled brain metastasis or mental illness.
7. Congestive heart failure, uncontrolled cardiac arrhythmia, etc.
8. Other malignancy within 5 years.
9. Can't be followed up or obey protocol.
10. Ineligible by the discretion of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AS：Nanoparticle albumin-bound paclitaxel，S-1	nanoparticle albumin-bound paclitaxel	Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 of each 14 day cycle. S-1 is orally administered (BSA\<1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2, 50mg bid, BSA\>1.5m2, 60mg bid) on day 1-7 of each 14 day cycle.
AG：Nanoparticle albumin-bound paclitaxel，Gemcitabine	nanoparticle albumin-bound paclitaxel	Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 and 8 of each 21 day cycle. Gemcitabine is given at 1000mg/m2 intravenously on day 1 and 8 of each 21 day cycle.
AS：Nanoparticle albumin-bound paclitaxel，S-1	S1	Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 of each 14 day cycle. S-1 is orally administered (BSA\<1.25m2, 40mg bid, 1.25m2≤BSA≤1.5m2, 50mg bid, BSA\>1.5m2, 60mg bid) on day 1-7 of each 14 day cycle.
AG：Nanoparticle albumin-bound paclitaxel，Gemcitabine	Gemcitabine	Nanoparticle albumin-bound paclitaxel is given at 125 mg/m2 intravenously on day 1 and 8 of each 21 day cycle. Gemcitabine is given at 1000mg/m2 intravenously on day 1 and 8 of each 21 day cycle.

Primary Outcome Measures

Name	Time	Method
Objective response rate	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)(every 3 cycles in AS or every 2 cycles in AG).

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to 2 years	Measure of time from study treatment to patient's death or lost to follow-up.
Objective response rate of primary tumor	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)(every 3 cycles in AS or every 2 cycles in AG).
Disease control rate	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	The sum of rates of partial response, complete response and steady disease based on Response Evaluation Criteria In Solid Tumors (RECIST).
Progression-free survival	up to 15 months	Measure of time from study treatment to disease progression or death.
The incidence of treatment related emergent adverse events（Safety and Tolerance）	Until 28 days after the deadline of enrollment	Adverse reactions evaluation is based on the National Cancer Institute adverse event General terminology Standard \[CTCAE\] 4.0 version

Trial Locations

Locations (1)

Peking University Cancer Hospital and Institute; 🇨🇳 Beijing, Beijing, China