Back to resultsSecond-Line Adjuvant Therapy With Nab-Paclitaxel Plus Gemcitabine Versus Oxaliplatin Plus Folinic Acid and Fluorouracil for Gemcitabine-Refractory Pancreatic Cancer After Curative Resection
Primary Purpose
Stage ⅠA Pancreatic Cancer, Stage ⅠB Pancreatic Cancer, Stage ⅡA Pancreatic Cancer
Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
nab-paclitaxel
gemcitabine
oxaliplatin
folinic acid
fluorouracil
Sponsored by
About this trial
This is an interventional treatment trial for Stage ⅠA Pancreatic Cancer focused on measuring Pancreatic Cancer, Pancreatic Adenocarcinoma, AG, OFF, Second-Line Adjuvant Therapy
Eligibility Criteria
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.
Sites / Locations
- Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center,Sun Yat-Sen UniversityRecruiting
- Department of Biliary Pancreatic Surgery, Shanghai Changzheng Hospital, The Second Military Medical UniversityRecruiting
- Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan UniversityRecruiting
- Department of Biliary Pancreatic Surgery, Huadong Hospital, Fudan UniversityRecruiting
- Department of Pancreatic Surgery, Huashan Hospital, Fudan UniversityRecruiting
- Department of Pancreatic Surgery, Cancer Institute & Hospital, Tianjin Medical UniversityRecruiting
- Department of General Surgery,Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
nab-paclitaxel + gemcitabine (AG)
oxaliplatin + folinic acid + fluorouracil (OFF)
Arm Description
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
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.
Outcomes
Primary Outcome Measures
Overall survival
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
Secondary Outcome Measures
Objective Response Rate
To evaluate the therapeutic efficacy of two regimens in terms of objective response rate. Computed tomography (CT) scan
Time to Remission
To evaluate the time to remission of patients treated with the two regimens. Computed tomography (CT) scan
Progression-Free Survival
To evaluate the progression-free survival of patients treated with the two regimens. Computed tomography (CT) scan
The Levels of Tumor Biomarkers in Serum
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
Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0
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.
Quality of life
To evaluate the quality of life score of patients treated with the two regimens. Outpatient visit, phone interview
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02506842
Brief Title
Second-Line Adjuvant Therapy With Nab-Paclitaxel Plus Gemcitabine Versus Oxaliplatin Plus Folinic Acid and Fluorouracil for Gemcitabine-Refractory Pancreatic Cancer After Curative Resection
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Unknown status
Study Start Date
June 2015 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
June 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage ⅠA Pancreatic Cancer, Stage ⅠB Pancreatic Cancer, Stage ⅡA Pancreatic Cancer, Stage ⅡB Pancreatic Cancer
Keywords
Pancreatic Cancer, Pancreatic Adenocarcinoma, AG, OFF, Second-Line Adjuvant Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
nab-paclitaxel + gemcitabine (AG)
Arm Type
Experimental
Arm Description
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
Arm Title
oxaliplatin + folinic acid + fluorouracil (OFF)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Other Intervention Name(s)
GEMZAR
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
folinic acid
Other Intervention Name(s)
LV
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Description
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
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).
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
To evaluate the therapeutic efficacy of two regimens in terms of objective response rate. Computed tomography (CT) scan
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).
Title
Time to Remission
Description
To evaluate the time to remission of patients treated with the two regimens. Computed tomography (CT) scan
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).
Title
Progression-Free Survival
Description
To evaluate the progression-free survival of patients treated with the two regimens. Computed tomography (CT) scan
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).
Title
The Levels of Tumor Biomarkers in Serum
Description
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
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).
Title
Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0
Description
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.
Time Frame
1 week during therapy and 3 months thereafter up to 24 months.
Title
Quality of life
Description
To evaluate the quality of life score of patients treated with the two regimens. Outpatient visit, phone interview
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xian-Jun Yu, M.D PH.D
Phone
+86 21 64175590
Email
yuxianjun@fudanpci.org
First Name & Middle Initial & Last Name or Official Title & Degree
Wen-Quan Wang, M.D PH.D
Phone
+86 21 64175590
Email
wangwenquan@fudanpci.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xian-Jun Yu, M.D PH.D
Organizational Affiliation
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center,Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng-Ping Li, M.D PH.D
Phone
020-87343088
Email
lishengp@mail.sysu.edu.cn
First Name & Middle Initial & Last Name & Degree
Sheng-Ping Li, M.D PH.D
Facility Name
Department of Biliary Pancreatic Surgery, Shanghai Changzheng Hospital, The Second Military Medical University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng-Hao Shao, M.D PH.D
Phone
021-81886999
Email
schhao88@gmail.com
First Name & Middle Initial & Last Name & Degree
Cheng-Hao Shao, M.D PH.D
Facility Name
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xian-Jun Yu, M.D., Ph.D.
Phone
+86-21-6417-5590
Email
yuxianjun@fudanpci.org
First Name & Middle Initial & Last Name & Degree
Wen-Quan Wang, M.D., Ph.D.
Phone
+86-21-6417-5590
Email
wangwenquan@fudanpci.org
First Name & Middle Initial & Last Name & Degree
Xianjun Yu, M.D., Ph.D.
Facility Name
Department of Biliary Pancreatic Surgery, Huadong Hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Wang, M.D PH.D
Phone
021-62483180
Email
wangw2003cn@hotmail.com
First Name & Middle Initial & Last Name & Degree
Wei Wang, M.D PH.D
Facility Name
Department of Pancreatic Surgery, Huashan Hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
De-Liang Fu, M.D PH.D
Phone
021-52889999
Email
surgeonfu@163.com
First Name & Middle Initial & Last Name & Degree
De-Liang Fu, M.D PH.D
Facility Name
Department of Pancreatic Surgery, Cancer Institute & Hospital, Tianjin Medical University
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ji-Hui Hao, M.D PH.D
Phone
022-23340123
Email
haojihui@tjmuch.com
First Name & Middle Initial & Last Name & Degree
Ji-Hui Hao, M.D PH.D
Facility Name
Department of General Surgery,Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi-Ping Mou, M.D PH.D
Phone
0571-86090073
Email
mouyp@srrsh.com
First Name & Middle Initial & Last Name & Degree
Yi-Ping Mou, M.D PH.D
12. IPD Sharing Statement
Learn more about this trial
Second-Line Adjuvant Therapy With Nab-Paclitaxel Plus Gemcitabine Versus Oxaliplatin Plus Folinic Acid and Fluorouracil for Gemcitabine-Refractory Pancreatic Cancer After Curative Resection
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