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.
|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.|
- 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.
|Study Start Date:||July 2006|
|Study Completion Date:||July 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
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.
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: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®
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|Principal Investigator:||Howard A. Burris, M.D.||SCRI Development Innovations, LLC|