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Neoadjuvant Chemotherapy and Digoxin for the Treatment of Resectable Pancreatic Cancer

Trial Status: Approved

This phase IIa trial studies how well neoadjuvant chemotherapy and digoxin work in treating patients with pancreatic cancer that can be removed by surgery (resectable). Drugs used in chemotherapy, such as fluorouracil, irinotecan, leucovorin calcium, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Digoxin may improve cancer drugs effect and slow tumor growth. Given neoadjuvant chemotherapy and digoxin together may work better in treating patients with resectable pancreatic cancer compared to chemotherapy alone.

Inclusion Criteria

  • Pathologically confirmed adenocarcinoma of the pancreas. Patients must have resectable disease with no evidence of distant metastasis
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
  • Patients who received chemotherapy for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 5 years ago and there is no evidence of the prior malignancy at the time of study entry
  • All patients must have radiographically assessable disease
  • Patients must have an initial absolute neutrophil count (ANC) greater than or equal to 1000/uL
  • Patients must have an initial platelet count greater than or equal to 100,000/uL
  • Patient must have normal serum potassium, magnesium and corrected calcium level
  • Patients must have a serum creatinine less than or equal to 2.0 mg/dL
  • Patients must have a total bilirubin =< 1.5 mg/dL (unless the patient has Gilbert disease with elevated non-conjugated (indirect) bilirubin; in such cases, the indirect bilirubin should be =< 1.0 mg/dL). If the patient has biliary obstruction, biliary decompression will be required. Either endoscopic placement of biliary stent or percutaneous transhepatic drainage are acceptable. Once biliary drainage has been established, institution of leucovorin calcium, 5-fluorouracil and oxaliplatin (FOLFOX) therapy may proceed when the total bilirubin falls to =< 5.0 mg/dL. The addition of irinotecan will be delayed until the total bilirubin is 1.5 mg/dL or lower
  • The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
  • No prior chemotherapy for pancreatic cancer

Exclusion Criteria

  • Patients who cannot undergo staging laparoscopy. For example, this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or might be potentially harmful
  • Patients with a contra-indication to receiving digoxin therapy, such as atrioventricular (AV) block, sick sinus syndrome, bradycardia, and hypersensitivity to digoxin or digitalis preparations
  • Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safety
  • Pregnant and nursing women are excluded from this study because of the risk posed by the chemotherapy agents. Female patients of childbearing potential must have a negative urine pregnancy test before receiving the first dose of study drug * Note: All subjects of reproductive potential must agree to use two barrier methods of birth control during the course of the study and for 6 months after the last dose of study drug(s).
  • Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
  • Patients with known human immunodeficiency virus (HIV) infection or active hepatitis B or C infection due to concern for increased toxicity
  • Patients with an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's disease, multiple sclerosis (MS), ankylosing spondylitis)
  • Patients with a recognized acquired, hereditary, or congenital immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia

Nebraska

Omaha
University of Nebraska Medical Center
Status: APPROVED
Contact: Jean Linette Grem
Phone: 402-559-8500

PRIMARY OBJECTIVE:

I. To assess the feasibility and safety of neoadjuvant chemotherapy with fluorouracil, irinotecan, leucovorin calcium, oxaliplatin (FOLFIRINOX) given with digoxin in patients with resectable pancreatic cancer.

SECONDARY OBJECTIVE:

I. To evaluate the efficacy of neoadjuvant chemotherapy with FOLFIRINOX given with digoxin in patients with resectable pancreatic cancer.

OUTLINE:

Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, leucovorin calcium IV over 90 minutes, and fluorouracil IV over 46 hours on day 1. Treatment repeats every 2 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive digoxin orally (PO) daily. Treatment repeats every 2 weeks for 4-8 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery. Patients may receive another 4 cycles of FOLFIRINOX chemotherapy after recovery from surgery.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Nebraska Medical Center

Principal Investigator
Jean Linette Grem

  • Primary ID 668-19
  • Secondary IDs NCI-2020-00007
  • Clinicaltrials.gov ID NCT04141995