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

Celgene

Status and phase: Completed; Phase 1

Conditions: Pancreatic Cancer

Treatments: Drug: Romidepsin; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00379639

GPI-06-0003

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Romidepsin / Gemcitabine

Experimental group

Description:

Participants were to receive 7, 10 or 12 mg/m\^2 of romidepsin intravenously on either Days 1, 8 and 15 (Schedule A) or Days 1 and 15 (Schedule B) of each 28-day cycle, followed by 800 or 1000 mg/m\^2 of gemcitabine. Subsequent doses of both drugs were based on treatment-related toxicities. The planned duration of study therapy was 6 cycles or until disease progression occurred. Patients who responded could continue beyond 6 cycles until disease progression or until a withdrawal criterion was met.

Treatment:

Drug: Gemcitabine

Drug: Romidepsin