Second-Line Adjuvant Therapy With Nab-Paclitaxel Plus Gemcitabine Versus Oxaliplatin Plus Folinic Acid and Fluorouracil for Gemcitabine-Refractory Pancreatic Cancer After Curative Resection

August 10, 2016 updated by: Xian-Jun Yu, Fudan University

A Prospective, Multi-centric, Phase Ⅲ, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Second-Line Adjuvant Therapy With Nab-Paclitaxel Plus Gemcitabine (AG) Versus Oxaliplatin Plus Folinic Acid and Fluorouracil (OFF) for Gemcitabine-Refractory Pancreatic Cancer After Curative Resection

The purpose of this study is to investigate the activity and safety of second-line adjuvant therapy with nab-paclitaxel plus gemcitabine (AG) versus oxaliplatin plus folinic acid and fluorouracil (OFF) for gemcitabine-refractory pancreatic cancer after curative resection.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

  • To evaluate the therapeutic efficacy of second-line adjuvant therapy with nab-paclitaxel plus gemcitabine (AG) versus oxaliplatin plus folinic acid and fluorouracil (OFF) in terms of overall survival for gemcitabine-refractory pancreatic cancer after curative resection.

SECONDARY OBJECTIVES:

  • To evaluate the therapeutic efficacy of two regimens in terms of objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • To evaluate the time to remission of patients treated with the two regimens.
  • To evaluate the progression-free survival of patients treated with the two regimens.
  • To evaluate the levels of tumor biomarkers in serum of patients treated with the two regimens, including Carbohydrate Antigen (CA)19-9、CA125、CA153、CA242、CA72-4、CA50、CEA、AFP.
  • To evaluate the occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Effects (NCI CTCAE) version 4.0 in patients treated with the two regimens.
  • To evaluate the quality of life score of patients treated with the two regimens.

Detailed Description of Arms:

Patients are randomized to 1 of 2 treatment arms (Arm AG or Arm OFF). Arm AG: Firstly, patients receive nab-paclitaxel 100 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment. Secondly, patients receive gemcitabine 1000 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment. Treatment repeats until there is disease progression or recurrence.

Arm OFF: Patients receive oxaliplatin 85 mg/m^2 (iv, 2 hours) on days 8 and 22 with 42 days as a cycle. Patients receive folinic acid 200 mg/m^2 (iv) and fluorouracil 2000 mg/m^2 (iv, 24 hours) on days 1, 8, 15 and 22 for 4 weeks, followed by 2 weeks without treatment. Oxaliplatin is given before folinic acid and fluorouracil when the three drugs are given on the same days. Treatment repeats until there is disease progression or recurrence.

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center,Sun Yat-Sen University
        • Contact:
        • Principal Investigator:
          • Sheng-Ping Li, M.D PH.D
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
      • Shanghai, Shanghai, China, 200003
        • Recruiting
        • Department of Biliary Pancreatic Surgery, Shanghai Changzheng Hospital, The Second Military Medical University
        • Contact:
        • Principal Investigator:
          • Cheng-Hao Shao, M.D PH.D
      • Shanghai, Shanghai, China, 200040
        • Recruiting
        • Department of Biliary Pancreatic Surgery, Huadong Hospital, Fudan University
        • Contact:
        • Principal Investigator:
          • Wei Wang, M.D PH.D
      • Shanghai, Shanghai, China, 200040
        • Recruiting
        • Department of Pancreatic Surgery, Huashan Hospital, Fudan University
        • Contact:
        • Principal Investigator:
          • De-Liang Fu, M.D PH.D
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Recruiting
        • Department of Pancreatic Surgery, Cancer Institute & Hospital, Tianjin Medical University
        • Contact:
        • Principal Investigator:
          • Ji-Hui Hao, M.D PH.D
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310016
        • Recruiting
        • Department of General Surgery,Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
        • Contact:
        • Principal Investigator:
          • Yi-Ping Mou, M.D PH.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Signed informed content obtained prior to treatment
  • Age ≥ 18 years and ≤ 75 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients must have histologically confirmed pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant) after R0 or R1 resection. The pathological staging does not exceed the stage ⅡB. And the patients have received gemcitabine as adjuvant chemotherapy after curative resection.
  • There is progression or recurrence of tumor during the course of adjuvant chemotherapy with gemcitabine, or within 6 months after the whole courses of treatment.
  • No severe defects in hematological system, immune system, cardiac function and pulmonary function.
  • White blood cell (WBC) ≥ 4 × 10^9/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelets (PLT) ≥ 100 × 10^9/L; Hemoglobin (Hgb) ≥ 9 g/dL
  • Aspartate aminotransferase (AST) (serum glutamate oxaloacetate transaminase (SGOT)）/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin (TBIL) ≤ ULN; Creatinine (CRE) ≤ 1.5 × ULN
  • Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN
  • The patients are willing to comply to the study plan and other requirements.

Exclusion Criteria:

  • There is another malignant tumor with the patient.
  • Patients who have received any form of anti-tumor therapy within 4 weeks prior to the enrollment, including chemotherapy, radiotherapy, interventional chemoembolization, radiofrequency ablation, and molecular targeted therapy
  • Use of any other investigational agents within 4 weeks prior to the enrollment.
  • The progression or recurrence of tumor occurs after 6 months of the course of the adjuvant chemotherapy with gemcitabine.
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to the drugs.
  • Metabolic acidosis, acute or chronic, including ketoacidosis
  • Pregnant or nursing women
  • Any event or condition that is possible to harm the safety of the patients or the integrities of data, including severe medical risk factors, medical conditions, and laboratory disorders.
  • Patients who are unwilling or unable to comply with study procedures, or may be absent from the observation for more than 7 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nab-paclitaxel + gemcitabine (AG)
nab-paclitaxel at 100 mg/m^2 on days 1, 8, and 15; gemcitabine at 1000 mg/m^2 on days 1, 8, and 15
Drug: nab-paclitaxel
Patients firstly receive nab-paclitaxel 100 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment. Treatment repeats until there is disease progression or recurrence.
Other Names:
  • Abraxane
Drug: gemcitabine
Patients secondly receive gemcitabine 1000 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment. Treatment repeats until there is disease progression or recurrence.
Other Names:
  • GEMZAR
Experimental: oxaliplatin + folinic acid + fluorouracil (OFF)
oxaliplatin at 85mg/m^2 on days 8 and 22, folinic acid at 200mg/m^2 on days 1,8,15 and 22, fluorouracil at 2000mg/m^2 on days 1,8,15 and 22.
Drug: oxaliplatin
Patients receive oxaliplatin 85 mg/m^2 (iv, 2 hours) on days 8 and 22 with 42 days as a cycle. Treatment repeats until there is disease progression or recurrence. Oxaliplatin is given before folinic acid and fluorouracil when the three drugs are given on the same days.
Drug: folinic acid
Patients receive folinic acid 200 mg/m^2 (iv) on days 1, 8, 15 and 22 for 4 weeks, followed by 2 weeks without treatment. Treatment repeats until there is disease progression or recurrence.
Other Names:
  • LV
Drug: fluorouracil
Patients receive fluorouracil 2000 mg/m^2 (iv, 24 hours) on days 1, 8, 15 and 22 for 4 weeks, followed by 2 weeks without treatment. Treatment repeats until there is disease progression or recurrence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: From date of enrollment until the date of death from any cause, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
To evaluate the therapeutic efficacy of second-line adjuvant therapy with AG versus OFF in terms of overall survival for gemcitabine-refractory pancreatic cancer after curative resection. Outpatient visit, phone interview
From date of enrollment until the date of death from any cause, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: Complete Remission% + Partial Remission %, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
To evaluate the therapeutic efficacy of two regimens in terms of objective response rate. Computed tomography (CT) scan
Complete Remission% + Partial Remission %, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
Time to Remission
Time Frame: From date of enrollment until the date of remission, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
To evaluate the time to remission of patients treated with the two regimens. Computed tomography (CT) scan
From date of enrollment until the date of remission, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
Progression-Free Survival
Time Frame: From date of enrollment until the date of first documented progression, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
To evaluate the progression-free survival of patients treated with the two regimens. Computed tomography (CT) scan
From date of enrollment until the date of first documented progression, assessed 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
The Levels of Tumor Biomarkers in Serum
Time Frame: 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
To evaluate the levels of tumor biomarkers in serum of patients treated with the two regimens, including Carbohydrate Antigen (CA)19-9、CA125、CA153、CA242、CA72-4、CA50、CEA、AFP . Outpatient visit, laboratory findings
2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0
Time Frame: 1 week during therapy and 3 months thereafter up to 24 months.
To evaluate the occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0) in patients treated with the two regimens. The toxicity profile includes but not limits neutropenia, thrombocytopenia, peripheral neuropathy, hypoglycemia, metabolic acidosis (acute or chronic, including ketoacidosis), which will be summarized as the percentage of patients by type and grade according to treatment group. Outpatient visit, laboratory findings.
1 week during therapy and 3 months thereafter up to 24 months.
Quality of life
Time Frame: 2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).
To evaluate the quality of life score of patients treated with the two regimens. Outpatient visit, phone interview
2 cycles during the therapy and 3 months thereafter up to 24 months; Cycle 1 (each cycle is 28 days for AG regimen and 42 days for OFF regimen).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Xian-Jun Yu, M.D PH.D, Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

July 18, 2015

First Submitted That Met QC Criteria

July 22, 2015

First Posted (Estimate)

July 23, 2015

Study Record Updates

Last Update Posted (Estimate)

August 11, 2016

Last Update Submitted That Met QC Criteria

August 10, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSPAC-010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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