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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00379639
First received: September 20, 2006
Last updated: July 5, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: Romidepsin
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Number of Participants With a Dose-limiting Toxicity (DLT) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

    Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), V 3.0. A DLT was one of the following, if considered at least possibly related to study treatment:

    Grade 4 neutropenia for ≥5 days or febrile neutropenia; Grade 4 thrombocytopenia or need for a platelet transfusion; ≥ Grade 3 nausea and/or emesis despite using optimal antiemetic therapy; ≥ Grade 3 diarrhea despite using maximal supportive therapy; Any clinically significant Grade 3 or 4 nonhematologic toxicity; Inability to administer all doses in cycle 1.


  • Number of Participants With Adverse Events (AEs) [ Time Frame: From the date of first dose to 30 days after last dose (up to 236 days). ] [ Designated as safety issue: Yes ]

    AEs were graded for severity according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), V 3.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe (prevents normal everyday activities); Grade 4: Life-threatening or disabling; Grade 5: Death.

    A serious AE is associated with events that pose a threat to a patient's life or functioning, require hospitalization, is a congenital anomaly/birth defect or is an important medical event or condition that may jeopardize the patient and may require medical or surgical intervention to prevent one of the above outcomes.


  • Best Overall Response [ Time Frame: Disease assessments were performed within 4 weeks of first dose and every 8 weeks thereafter (up to 236 days). ] [ Designated as safety issue: No ]

    Disease response was determined by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria using computed tomography or magnetic resonance imaging:

    Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions or the appearance of ≥1 new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.



Enrollment: 36
Study Start Date: July 2006
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Romidepsin / Gemcitabine
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.
Drug: Romidepsin
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.
Other Names:
  • ISTODAX®
  • Depsipeptide
  • FK228
Drug: Gemcitabine
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.
Other Name: Gemzar®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00379639

Locations
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Howard A. Burris, M.D. SCRI Development Innovations, LLC
  More Information

Publications:
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00379639     History of Changes
Other Study ID Numbers: GPI-06-0003
Study First Received: September 20, 2006
Results First Received: July 5, 2012
Last Updated: July 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Pancreatic cancer
advanced solid tumors

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Romidepsin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on September 18, 2014