A Phase II Trial to Assess the Evolution of KRAS Mutation Load by Liquid Biopsy in Patients With Resectable Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant NALIRINOX
NALRINOX combination
Treatment Study
Summary
Study start date: May 1, 2019
Actual date on which the first participant was enrolled.Pancreatic cancer has an unfavorable prognosis with a reduced possibility of long-term survival. The only treatment with curative potential is surgery, but it is only possible in 15-20% of cases. There are patients with clear criteria for surgical entry, others at the limit of the possibility of surgery, and patients with such advanced disease (either locally or with metastasis) that surgery is not indicated. The objective of neoadjuvant chemotherapy treatment (received before surgery) is to reduce the tumor before surgery and reduce the risk of subsequent metastases and local recurrences, in borderline tumors or those resectable with high-risk criteria. The FOLFIRINOX scheme, composed of 5-fluorouracil / folinic acid, oxaliplatin and irinotecan, is recommended as neoadjuvant treatment, but the response is still low. This study will use a modified FOLFIRINOX (NALIRINOX) regimen with a form of irinotecan attached to liposomes that allows greater action on tumor cells. Mutations in the KRAS gene are associated with a greater growth capacity of tumor cells and are present in 90% of pancreatic cancers in advanced stages. They would be less frequent in earlier phases but little is known about the impact that chemotherapy treatment and subsequent surgery could have on the increase or decrease of these mutations, as well as their implication. The follow-up of these mutations with repeated pancreatic biopsies is not viable, but it can be monitored by simple blood samples in which the genetic material of the tumor can be analyzed.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.20 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Criteria
Inclusion Criteria: 1. Male or females, aged 18 years or older 2. Histologically or cytologically confirmed diagnosis of PDAC 3. Candidates for pancreatic cancer surgery (no comorbidities that can exclude for surgery) 4. Life expectance of at least 12 months 5. Carbohydrate antigen 19-9 (CA19-9) levels \< 500 U/ml 6. ECOG performance status ≤ 1 7. Adequate bone marrow function: * Hemoglobin \>9 g/dL * Platelets \>100.000 µL * Absolute neutrophil count (ANC) \>1500 µl * Serum albumin \> 3 g/dL 8. Adequate hepatic function: * Aspartate aminotransferase (AST) \<3 upper limits of normal (ULN) * Alanine Aminotransferase (ALT) \<3 ULN * Total Bilirubin \< 1.5 ULN. If values are \> 1.5 external drainage with a stent is allowed. 9. Adequate renal function: \- Clearance of creatinine (ClCr) \>60 ml/min 10. Sexually active men and women of childbearing potential must use efficient contraceptive methods. Contraceptive methods comprise: oral contraceptives, intrauterine devices, sexual abstinence, tubal ligation, IUD, barrier methods or another contraceptive considered appropriate by the investigator. Women of childbearing potential must have a negative serum pregnancy test before study entry. 11. Agree to participate and signed the ICF. Exclusion Criteria: 1. Patients with metastatic disease 2. Patients ≥ 75 years. 3. Uncontrolled coagulopathy 4. Patients with a contraindication to surgery (locally advanced disease or patients not amenable to pancreatic surgery due to a previous comorbidity) 5. Patients with prior or concurrent malignant disease that required treatment with chemotherapy in the past. 6. Previous cytotoxic therapy within 36 months for other no-cancer disease (ie arthritis rheumatoid) 7. Known or suspected reactions to any component of the study medication (5-FU/LV, nal- IRI or oxaliplatin) or to components of similar chemical or biologic composition 8. Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule 9. Human immunodeficiency virus (HIV) positivity, active Hepatitis B or Hepatitis C infection. 10. Uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, myocardial infarction, or left ventricular ejection fraction (LVEF) \< 50, among others, or psychiatric illness/social situations that would limit compliance with study requirements. 11. Pregnant or breast-feeding women. 12. Any medical condition that, based on investigator's criteria, places the subject at risk, makes the subject ineligible or may jeopardize protocol compliance.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 3 locations
Hospital Universitario Madrid Sanchinarro
PAU de Sanchinarro, SpainHospital Universitari Vall D'Hebron
Barcelona, Spain