Clinical trial NCT03585062: Trial of Neoadjuvant Chemotherapy With S1 Plus Paclitaxel-albumin on Pancreatic Cancer
Official title: Clinical Trial of Neoadjuvant Chemotherapy With S1 Plus Paclitaxel-albumin in Patients With Unresectable Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Neoadjuvant Chemotherapy
Keywords: S-1
Paclitaxel-albumin
Unresectable Pancreatic Cancer
Neoadjuvant chemotherapy
Lead sponsor: Zhejiang Provincial People's Hospital
Sponsor class: OTHER
First posted: 2018-07-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is to evaluate the R0 resection rate of patients with unresectable locally advanced pancreatic cancer ,after treated with S-1 plus Paclitaxel-albumin as neoadjuvant chemotherapy protocols

Detailed description: BACKGROUND:

1. The incidence of pancreatic cancer in China has been increasing rapidly in recent years，but most of the pancreatic cancer patients are unresectable, whose median survival time were only 6\~9 months.
2. Studies have shown that neoadjuvant therapy improves the quality of surgery in patients with pancreatic cancer，and prolong their life.
3. S-1 is a new generation of oral fluorouracil derivatives ,S-1 single drug as an adjuvant therapy for resectable pancreatic cancer is better than gemcitabine, and has less side effects than gemcitabine. Protein bound paclitaxel is a novel paclitaxel combined of paclitaxel and albumin by nanotechnology , which can extend free survival in patients with advanced pancreatic cancer with less side effects than gemcitabine. So S-1 combined with Paclitaxel-albumin is expected to play an important role in neoadjuvant chemotherapy in Pancreatic cancer, and may improve the rate of R0 resection in patients with unresectable locally advanced pancreatic.

STUDY DESIGN:

S-1 combined with Paclitaxel-albumin

1. S-1:40\~60mg bid, day 1\~14 (S-1: BSA (Body surface area)\<1.25m2, 40mg bid , 1.25m2 ≤ BSA ≤1.5m2, 50mg bid, BSA\>1.5m2, 60mg bid),2 weeks and rest for 1 weeks.
2. Paclitaxel-albumin: 125 mg/m2, intravenous infusion for 30 minutes, Day1 and Day 8.

Repeat every three weeks. for 6 cycles.

Eligibility criteria: Inclusion Criteria:

1. Confirmed invasive ductal adenocarcinoma of pancreas by histology
2. Evaluated as CT4N0M0 pancreatic cancer patients by Image testing
3. Adults age from 18-80 years old
4. No history of pancreatic resection or pancreatic cancer
5. ECOG score 0-1; can be orally administered
6. No distant metastasis or malignant ascites
7. Relatively good liver、 kidney、heart、hematology function. Baseline blood routine and biochemical indexes of the subjects meet the following criteria: hemoglobin ≥90g/L;absolute neutrophil count(ANC)≥3.5×109/L；Platelet≥100×109/L;prothrombin time ≤1.8;partial thromboplastin time ≤1.8; ALT≤102U/L、AST≤95U/L; ALP≤2.5 times the upper limits of normal; Serum total bilirubin≤2.5 g/dL(total bilirubin ≤1.5 times the upper limit of normal (ULN)；Serum creatinine≤2.0 mg/dL； creatinine clearance rate \>50 ml/min
8. Sign the Informed consent -

Exclusion Criteria:

1. Woman in pregnant or lactation period
2. Woman of childbearing age who was positive at baseline pregnancy test or did not have pregnancy tests.Menopausal women must have menopause for at least 12 months before they think they are free of pregnancy.
3. Men and women who had sexual life (Fertility possibility) were reluctant to have contraception during the study period.
4. Patients with the history of other malignant diseases in the past 5 years, except for cured skin cancer and cervical carcinoma in situ.
5. Patients of uncontrolled epilepsy, central nervous system diseases or history of mental disorders, should be judged by the researchers whether their clinical severity hinder the signature of the informed consent or influenced patients'compliance with oral medications
6. Clinically serious (i.e. activity) heart disease, such as symptomatic coronary heart disease , New York Heart Association (NYHA) class II or more serious congestive heart failure or serious arrhythmia which need drug intervention, or have a history of MI within the last 12 months.
7. Patients with upper gastrointestinal obstruction or Abnormal physiological function or Malabsorption syndrome, which may affect the absorption of S-1.
8. Organ transplant patients who need immunosuppressive therapy
9. Patients with Serious uncontrolled repeated infection or other serious uncontrolled Concomitant disease.
10. Patient that is lack of dihydropyrimidine dehydrogenase (DPD)
11. Allergic to any of the drug ingredients in this study
12. participate in other clinical trials within 4 weeks before randomization -

Primary outcomes:
measure: R0 resection rate
timeFrame: one week After the operation
Secondary outcomes:
measure: The objective remission rate (ORR)
timeFrame: at the end of cycle 6 of the neoadjuvant chemotherapy((each cycle is 21 days)
measure: The disease free survival (DFS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first,assessed up to 60 months. Progressing should be confirmed by imaging examination or histology / cytology examination.
measure: The 2 year and 5 year survival rate
timeFrame: 2 years and 5 years after treatment
measure: The quality of life
timeFrame: Questionnaire at baseline, and then 1-2 days before each cycle of treatment(each cycle is 21 days, for a total of 6 cycles.). During follow-up period after treatment, questionnaire every 6 months, up to 2 years.
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: Zhejiang procincial people's hospital
state: Zhejiang
Study officials:
References:
citation: Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.
citation: Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.
citation: Witkowski ER, Smith JK, Tseng JF. Outcomes following resection of pancreatic cancer. J Surg Oncol. 2013 Jan;107(1):97-103. doi: 10.1002/jso.23267. Epub 2012 Sep 18.
citation: Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Buchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18;350(12):1200-10. doi: 10.1056/NEJMoa032295.