Back to resultsA Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Romidepsin
Gemcitabine
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring Pancreatic cancer, advanced solid tumors
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
Sites / Locations
- Sarah Cannon Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Romidepsin / Gemcitabine
Arm 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.
Outcomes
Primary Outcome Measures
Number of Participants With a Dose-limiting Toxicity (DLT)
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)
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
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00379639
Brief Title
A Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors
Official Title
A Phase I/II Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
July 1, 2006 (Actual)
Primary Completion Date
July 1, 2008 (Actual)
Study Completion Date
July 1, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
Pancreatic cancer, advanced solid tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Romidepsin / Gemcitabine
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Romidepsin
Other Intervention Name(s)
ISTODAX®, Depsipeptide, FK228
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With a Dose-limiting Toxicity (DLT)
Description
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.
Time Frame
28 days
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
From the date of first dose to 30 days after last dose (up to 236 days).
Title
Best Overall Response
Description
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.
Time Frame
Disease assessments were performed within 4 weeks of first dose and every 8 weeks thereafter (up to 236 days).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Howard A. Burris, M.D.
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22536933
Citation
Jones SF, Infante JR, Spigel DR, Peacock NW, Thompson DS, Greco FA, McCulloch W, Burris HA 3rd. Phase 1 results from a study of romidepsin in combination with gemcitabine in patients with advanced solid tumors. Cancer Invest. 2012 Jul;30(6):481-6. doi: 10.3109/07357907.2012.675382. Epub 2012 Apr 26.
Results Reference
result
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A Study of Romidepsin (Depsipeptide) in Combination With Gemcitabine in Patients With Pancreatic and Other Advanced Solid Tumors
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