A Study of Administering FOLFIRINOX Before Surgery For Potentially Curable Pancreatic Cancer

• Status: Unknown status
• Trial end date: 2018-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Pancreatic cancer is a serious condition and is one of the leading cause of cancer related health problem. It is estimated that in 2016, 5,200 Canadians will be diagnosed with pancreatic cancer, and approximately 20% (1 in 5) of patients will have localized cancer (cancer that is limited to pancreas and there is no evidence of cancer in other parts of the body). Localized cancer is earlier stage of disease and surgery to remove the cancer is standard of care in this condition. However, recent scientific and clinical studies show that using the chemotherapy medication before surgery can improve the overall survival in patents with localized pancreatic cancer. One of these chemotherapy regimen is combination of fluorouracil, oxaliplatin, irinotecan, leucovorin (FOLFIRINOX) that we are going to evaluate its effect in this study.

Because of promising result of this combination in more advanced stage of pancreatic cancer, this study is going to examine its efficiency in earlier stage of pancreatic cancer (localized form). Total number of participant in this study will be 20 patients with localized form of pancreatic cancer without any evidence of cancer in other parts of the body.

Laboratory tests show that it works by slowing down the growth of cancer or may cause cancer cells to die. It is hoped that by shrinking the tumor size, the surgeon will be able to remove the cancer and improve the overall survival.

Procedures start with 2 weeks of comprehensive evaluation. Approximately 20 eligible subjects, based on this study criteria, will receive 6 treatment of this regimen every 2 weeks. Once 6 treatments have been completed, comprehensive re-evaluation procedures will be repeated, and subjects without disease progression or unacceptable toxicity will continue on their treatment based on treating team decision (surgical intervention, radiation therapy or continue FOLFIRINOX or different regimen). Patients then will follow with CT scan, blood test and physical examination every 3 months.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Petr Kavan
• Treatments: Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• Subjects must satisfy the following criteria to be enrolled in the study:

1. ≥ 18 years of age at the time of signing the informed consent form.

2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures conducted.

3. Histologically or cytologically confirmed adenocarcinoma of the pancreas.

4. Performance status or Comorbidity condition not currently appropriate (but potentially reversible) for a major abdominal operation.

Acceptable hematology parameters:

1. Absolute neutrophil count (ANC) ≥ 1500 cell/mm3

2. Platelet count ≥ 100,000/mm3 without transfusion support.

3. Hemoglobin (Hgb) ≥ 9 g/dL

Acceptable blood chemistry levels:

1. Hepatic transaminases (ALT and AST) less than 2.5× the upper limits of normal (ULN)

2. Total bilirubin level less than 1.5 × the upper limits of normal (ULN) or in patient with Biliary stenting less than 2 mg/dL

3. Serum creatinine level less than 1.5 × the upper limits of normal (ULN) or creatinine clearance (Ccr) ≥ 40 mL/min.

4. Alkaline phosphatase ≤ 2.5 x ULN

5. Serum albumin > 3 g/dL

Absence of poorly controlled comorbid conditions:

1. Congestive heart failure (CHF)

2. Chronic obstructive pulmonary disease (COPD)

3. Uncontrolled diabetes mellitus (DM)

4. Neurologic disorders (not acutely related to pancreatic cancer) or limit function

5. Radio-graphically suspicious but not diagnostic for extra-pancreatic disease,

1. Superior mesenteric vein and portal vein confluence that can be reconstructed even if short segment venous occlusion is present (i.e. a suitable portal vein above, and a suitable Superior mesenteric vein below the area of occlusion);

2. Tumor abutment of the Superior mesenteric artery of ≤180⁰,

3. Short segment encasement of the hepatic artery amenable to resection and reconstruction (this is usually at the origin of the gastroduodenal artery and reconstruction may or may not require interposition grafting with a short segment of reversed saphenous vein).

6. Cancer antigen 19-9 level (in absence of jaundice) ≥ 100u/ml suggestive of disseminated disease.

7. Preoperative treatment is recommended as an alternative for patients with potentially curable pancreatic cancer who meet all of the following criteria:

no clinical evidence for metastatic disease, a performance status and comorbidity condition appropriate for a major abdominal operation, no radiographic interface between primary tumor and mesenteric vasculature on imaging, an acceptable Cancer antigen 19-9 level.

Exclusion Criteria:

• The presence of any of the following will exclude a subject from enrollment:

1. Pancreatic tumors of endocrine or mixed origin.

2. Prior anticancer therapy for pancreatic carcinoma.

3. Presence of or history of metastatic pancreatic adenocarcinoma.

4. Any other malignancy within 5 years prior to enrollment, with the exception of adequately treated in-situ carcinoma of the prostate (Gleason score ≤ 7), cervix, uteri, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment).

5. Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.

6. Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelo-suppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications.

7. History of allergy or hypersensitivity to study regimen or any of their excipients.

8. Peripheral sensory neuropathy Grade > 1.

9. Clinically significant ascites.

10. Plastic biliary stent. (Metal biliary stent is allowed.)

11. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the integrity of the study data. These include, but are not limited to:

1. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa)

2. History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or multiple allergies

3. History of the following within 6 months prior to treatment 1 Day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder

12. Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures.

13. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

14. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

15. Any condition that confounds the ability to interpret data from the study.

16. Unwillingness or inability to comply with study procedures.

17. Pregnant or breast feeding.