Phase 2A Pilot Trial of Metformin, Digoxin, Simvastatin (C3) in Combination With Gemcitabine in Subjects With Recurrent / Refractory Metastatic Advanced Pancreatic Cancer
State University of New York - Downstate Medical Center
Summary
The goals of this trial are: 1) To evaluate the safety and tolerability of C3 administration with Gemcitabine; and 2) To assess the disease response following C3 administration with Gemcitabine. The main question it aims to answer are: 1) Is C3 in combination with Gemcitabine safe, tolerable, and effective for reducing improving advanced stage pancreatic cancer? and 2) Can C3 in combination with Gemcitabine prolong the lives of patients with advanced stage pancreatic cancer. Participants will receive a combination of metformin (850 mg twice a day), digoxin (0.25 mg once a day), and simvastatin (20 mg once a day), also known as C3, and Gemcitabine (as per standard of care) for 2 years. If patients decline Gemcitabine, they will be offered the C3 medications only.
Description
Background. Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest cancers and ranks fourth in cancer-related deaths in the United States. It is among the 10 most commonly diagnosed cancers (9th in women and 10th in men), with approximately 56,770 new cases and 45,750 deaths in 2019. Current therapy for advanced disease includes the use of medications such as Gemcitabine, Erlotinib, Capecitabine, or combination treatments such as 5-fluorouracil, irinotecan, and oxaliplatin; or Gemcitabine and nab-paclitaxel. These standard of care medications have a survival advantage of less than six…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Subject ≥18 years with histologically confirmed pancreatic cancer. 2. Refractory, intolerant to, or with disease progression after at least one standard of care regimen. 3. ECOG performance status (PS) 0-1. 4. Pretreatment biopsy and/or adequate archival tissue available for BIRC5 protein level evaluation. 5. Adequate organ and marrow function: absolute granulocyte count ≥1,000/mm3, platelets ≥100,000/mm3, total bilirubin ≤ institutional upper normal limit, AST/ALT ≤2x institutional upper limit of normal, and creatinine \<1.5 mg/dL or calculated creatinine clearance \>…
Interventions
- DrugGemcitabine and C3 (Metformin, Simvastatin, and Digoxin)
Combination treatment of Metformin, Simvastatin and Digoxin with Gemcitabine (Arm 1)
- DrugC3 (Metformin, Simvastatin, and Digoxin) only
C3 only (Metformin, Simvastatin, and Digoxin) if patients decline Gemcitabine (Arm 2).
Location
- SUNY Downstate Health Sciences UniversityBrooklyn, New York