Clinical trial NCT02506842: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: 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
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2015-07-23
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall survival
timeFrame: 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 outcomes:
measure: Objective Response Rate
timeFrame: 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).
measure: Time to Remission
timeFrame: 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).
measure: Progression-Free Survival
timeFrame: 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).
measure: The Levels of Tumor Biomarkers in Serum
timeFrame: 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).
measure: Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0
timeFrame: 1 week during therapy and 3 months thereafter up to 24 months.
measure: Quality of life
timeFrame: 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).
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center,Sun Yat-Sen University
state: Guangdong
city: Shanghai
country: China
facility: Department of Biliary Pancreatic Surgery, Shanghai Changzheng Hospital, The Second Military Medical University
state: Shanghai
city: Shanghai
country: China
facility: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Department of Biliary Pancreatic Surgery, Huadong Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Department of Pancreatic Surgery, Huashan Hospital, Fudan University
state: Shanghai
city: Tianjin
country: China
facility: Department of Pancreatic Surgery, Cancer Institute & Hospital, Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: Department of General Surgery,Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China
name: Xian-Jun Yu, M.D PH.D
role: PRINCIPAL_INVESTIGATOR
References: