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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02506842
Other study ID # CSPAC-010
Secondary ID
Status Recruiting
Phase Phase 3
First received July 18, 2015
Last updated August 10, 2016
Start date June 2015
Est. completion date June 2019

Study information

Verified date August 2016
Source Fudan University
Contact Xian-Jun Yu, M.D PH.D
Phone +86 21 64175590
Email yuxianjun@fudanpci.org
Is FDA regulated No
Health authority China: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 300
Est. completion date June 2019
Est. primary completion date December 2018
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 75 Years
Eligibility 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 ?B. 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

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.
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.
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.
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.
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.

Locations

Country Name City State
China Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center,Sun Yat-Sen University Guangzhou Guangdong
China Department of General Surgery,Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang
China Department of Biliary Pancreatic Surgery, Huadong Hospital, Fudan University Shanghai Shanghai
China Department of Biliary Pancreatic Surgery, Shanghai Changzheng Hospital, The Second Military Medical University Shanghai Shanghai
China Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University Shanghai Shanghai
China Department of Pancreatic Surgery, Huashan Hospital, Fudan University Shanghai Shanghai
China Department of Pancreatic Surgery, Cancer Institute & Hospital, Tianjin Medical University Tianjin Tianjin

Sponsors (1)

Lead Sponsor Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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). No
Secondary 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). No
Secondary 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). No
Secondary 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). No
Secondary 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). No
Secondary 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. Yes
Secondary 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). No