Efficacy and Safety of Nab-Paclitaxel Plus S-1 in the First-line Treatment of Advanced Pancreatic Cancer

Efficacy and Safety of Nab-Paclitaxel Plus S-1 in the First-line Treatment of Advanced Pancreatic Cancer: A Pilot Single Arm Phase II Study

Pancreatic cancer is a common malignancy of digestive system with gradually increasing incidence, is the fourth and seventh leading cause of cancer-related mortality in the world (1) and China (2) according to the statistics in 2014. The vast majority of patients were confirmed as locally advanced or distantly metastatic disease at diagnosis with an estimated five-year survival rate of 4% (3) due to occlusive development and rapid progress. Advanced pancreatic cancer is characterized by poor prognosis.

Study Overview

• Status: Completed
• Conditions: Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: Nab-paclitaxel and S-1

Detailed Description

Gemcitabine has been approved as the standard chemotherapy for advanced pancreatic cancer since 1996, but the efficacy is extremely limited by a response rate of 6-8%, and median survival of 5.5-7 months. However, Gemcitabine-based combination treatments fail to transcend GEM monotherapy on overall survival, including GEM + 5-Fu [10], GEM + Oxaliplatin[11], and GEM + Irinotecan [12] and GEM + Cisplatin [13] (7-8) . Until 2011, Conroy et al.[15] reported that FOLFIRINOX solutions significantly improved ORR (31.6% vs 9%, P=0.0008), PFS (6.4 vs. 3.3 months, P<0.0001) and OS (11.1 vs. 6.8 months, P<0.001) than GEM single-agent, but the significant increase of grade 3/4 adverse reactions, to some extent, limited its wide application. Therefore, it is necessary to continue to explore effective and safe chemotherapy of advanced pancreatic cancer.

Nab-Paclitaxel was approved by FDA for advanced pancreatic cancer in September 2013. S-1 has demonstrated potential value in the treatment of advanced pancreatic cancer as a new compound oral 5-FU(4-5) and has been approved for pancreatic cancer treatment in Japan.

We conducted a single arm, prospective, phase II study in our center on the first-line treatment of advanced pancreatic cancer with nab-Paclitaxel and S-1 to investigate the efficacy and safety of the combination regimen.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age, years: 18-75
• Histologically and cytologically confirmed advanced pancreatic cancer , inresectable, measurable lesions according to RECIST criteria; ECOG score of 0-1; life expectancy ≥12 weeks;
• Untreated; more than 6 months after the last adjuvant chemotherapy (does not include taxanes and S1);
• Laboratory examination within 14 days before entering the study should meet following requirements: ANC ≥ 1.5 x 10^9/L; PLT ≥ 100 x 10^9/L; Hb ≥ 90g/L (9g/dL); AST, ALT ≤ 2.5 x ULN (with no liver metastasis), ≤ 5 x ULN（with liver metastasis); creatinine ≤ 1.5 x ULN; TBIL ≤ 1.5 x ULN
• Both male and female subjects of potential fertility have to agree effective birth control during the entire study
• Informed consent

Exclusion Criteria:

• Concurrent other effective treatment (including radiotherapy)
• Resectable patients
• Allergy history to other drugs in the same class patients with pregnancy or lactation
• Known severe internal medical diseases
• Abnormal heart function or relevant history of myocardial infarction and severe arrhythmia
• Immunocompromised patients, such as HIV positive
• Uncontrollable mental illness
• Other conditions the researchers considered ineligible for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nab-paclitaxel Plus S-1; Nab-paclitaxel 120 mg/m2 (D1, D8, q3w) S-1 (40mg BID for body surface area<1.25 m2; 50mg BID for body surface area of 1.25-1.5m2; and 60mg BID for body surface area>1.5 m2; D1-14, q3w)	Drug: Nab-paclitaxel and S-1; Nab-paclitaxel 120 mg/m2 (D1, D8, q3w) and S-1 (40mg BID for body surface area < 1.25 m2; 50mgBID for body surface area of 1.25-1.5 m2; and 60mg BID for body surface area >1.5 m2; D1-14, q3w); Other Names: Abraxane,Tegafur, Gimeracil and Oteracil Porassium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate（ORR）	CR+PR was defined as objective response rate (ORR)	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	CR+PR+SD was defined as disease control rate (DCR)	6 month
PFS	From date of randomization until date of first documented PD, date of death	6 month
OS	From date of randomization until date of death	1 year
Safety profile: Adverse events of nab-Paclitaxel plus S-1 for advanced pancreatic cancer	Adverse events of nab-Paclitaxel plus S-1 for advanced pancreatic cancer	1 year

Collaborators and Investigators

• Sponsor: AIPING ZHOU
• Investigators: Principal Investigator: Aiping Zhou, Doctor, National Cancer Center/Cancer Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2015
• Primary Completion (Actual): July 11, 2017
• Study Completion (Actual): July 11, 2019

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: January 29, 2018
• First Posted (Actual): January 30, 2018

Study Record Updates

• Last Update Posted (Actual): February 1, 2021
• Last Update Submitted That Met QC Criteria: January 29, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: S-1; Advanced Pancreatic Cancer; Nab-Paclitaxel
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Tegafur
• Other Study ID Numbers: CH-GI-062

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No