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

Study Overview

Second-Line Adjuvant Therapy With Nab-Paclitaxel Plus Gemcitabine Versus Oxaliplatin Plus Folinic Acid and Fluorouracil 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.

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.

Stage ⅠA Pancreatic Cancer
Stage ⅠB Pancreatic Cancer
Stage ⅡA Pancreatic Cancer
Stage ⅡB Pancreatic Cancer

DRUG: nab-paclitaxel
DRUG: gemcitabine
DRUG: oxaliplatin
DRUG: folinic acid
DRUG: fluorouracil

CSPAC-010

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-07-18	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2016-08-10
First Submitted that Met QC Criteria 2015-07-22	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2016-08-11
First Posted (ESTIMATED) 2015-07-23	Results First Posted N/A	Last Verified 2016-08

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

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. 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.
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 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. 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.

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.

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.

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

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.

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.

Primary Outcome Measures	Measure Description	Time Frame
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	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	Measure Description	Time Frame
Objective Response Rate	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	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	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	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	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	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).

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

Name: Xian-Jun Yu, M.D PH.D

Phone Number: +86 21 64175590

Email: yuxianjun@fudanpci.org

Study Contact Backup

Name: Wen-Quan Wang, M.D PH.D

Phone Number: +86 21 64175590

Email: wangwenquan@fudanpci.org

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

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

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 A

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