A Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors

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