A Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Romidepsin; Gemcitabine
Intervention description: 7, 10 or 12 mg/m^2 via intravenous infusion over 4 hours on either Days 1, 8 and 15 or Days 1 and 15 of each 28-day cycle.; 800 or 1000 mg/m^2 via intravenous infusion over 30 minutes on either Days 1,8 and 15 or Days 1 and 15 of each 28 day cycle.
Intervention MeSH terms: Gemcitabine; Romidepsin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic cancer; advanced solid tumors

Summary:

      This was a phase I dose escalation trial designed to determine the maximum tolerated dose
      (MTD) for the combination of romidepsin (depsipeptide) and gemcitabine. The study was
      originally planned as a Phase I/II; however only Phase I of the study was conducted.
    

Eligibility criteria:

        Inclusion Criteria:

          -  histologically confirmed advanced solid tumors

          -  measurable or evaluable disease

          -  written informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

        Exclusion Criteria:

          -  Prior treatment with romidepsin or gemcitabine

          -  Prior chemotherapy treatment within 3 weeks prior to the first day of treatment or
             prior treatment with an investigational agent within 4 weeks prior to the first day of
             treatment. Patients must have recovered from all therapy-related toxicities (Common
             Terminology Criteria grade ≤ 1)

          -  Prior radiotherapy within 4 weeks prior to the first day of treatment. Patients who
             have not fully recovered or whose acute toxicity related to prior radiotherapy has not
             returned to baseline are ineligible.

          -  Prior surgery within 3 weeks prior to the first day of treatment, excluding surgical
             biopsies and port placements

          -  Concomitant use of any other anti-cancer therapy

          -  Concomitant use of any investigational agent

          -  Use of any investigational agent within 4 weeks of study entry

          -  Any known cardiac abnormalities, including congenital long QT syndrome, QTcF interval
             >480 milliseconds, myocardial infarction within 12 months of study entry, coronary
             artery disease (CAD), congestive heart failure (CHF), evidence of cardiac ischemia at
             screening, known history of sustained ventricular tachycardia (VT), ventricular
             fibrillation (VF), Torsade de Pointes, or cardiac arrest, hypertrophic cardiomegaly or
             restrictive cardiomyopathy chronic hypertension, any cardiac arrhythmia requiring
             anti-arrhythmic medication

          -  Serum potassium <3.8 mmol/L or serum magnesium <2.0 mg/dL (electrolyte abnormalities
             can be corrected with supplementation to meet inclusion criteria)

          -  Concomitant use of drugs that may cause a prolongation of the QTc

          -  Concomitant use of CYP3A4 inhibitors

          -  Clinically significant active infection

          -  Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

          -  Inadequate bone marrow or other organ function as evidenced by:

               -  Hemoglobin <9 g/dL (Transfusions and/or erythropoietin are permitted.)

               -  Absolute neutrophil count (ANC) ≤1.5 x 10^9 cells/L

               -  Platelet count <100 x 10^9 cells/L or platelet count <75 x 10^9 cells/L if bone
                  marrow disease involvement is documented

               -  Total bilirubin >2.0 x upper limit of normal (ULN)

               -  Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and
                  alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 x ULN or
                  >3.0 x ULN in the presence of demonstrable liver metastases

               -  Serum creatinine >2.0 x ULN

          -  Patients who are pregnant or breast-feeding

          -  Any significant medical or psychiatric condition that might prevent the patient from
             complying with all study procedures