A Study of Romidepsin (Depsipeptide) in Combination With... | NCT00379639

NCT00379639

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Romidepsin / Gemcitabine	Experimental	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 Drug: Gemcitabine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Romidepsin	Drug	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.	Romidepsin / Gemcitabine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	28 days
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.	From the date of first dose to 30 days after last dose (up to 236 days).
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.	Disease assessments were performed within 4 weeks of first dose and every 8 weeks thereafter (up to 236 days).

Eligibility Module

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

Name	Affiliation	Role
Howard A. Burris, M.D.	SCRI Development Innovations, LLC	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Sarah Cannon Research Institute		Nashville	Tennessee	37203	United States

PubMed Identifier	Type	Citation	Retractions
22536933	Result	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.

Arm/Group Information

ID	Title	Description
FG000	Dose Level 1	Participants received romidepsin 10 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1, 8, and 15 every 28 days.
FG001	Dose Level 2	Participants received romidepsin 7 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1, 8, and 15 every 28 days.
FG002	Dose Level 5	Participants received romidepsin 10 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1 and 15 every 28 days.
FG003	Dose Level 6	Participants received romidepsin 10 mg/m^2 plus gemcitabine 1000 mg/m^2 on Days 1 and 15 every 28 days.
FG004	Dose Level 8	Participants received romidepsin 12 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1 and 15 every 28 days.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0007 subjectsRepresents the number of patients who received any amount of study drug. FG0017 subjectsRepresents the number of patients who received any amount of study drug. FG00210 subjectsRepresents the number of patients who received any amount of study drug. FG0036 subjectsRepresents the number of patients who received any amount of study drug. FG0046 subjectsRepresents the number of patients who received any amount of study drug.
Efficacy Evaluable Population		FG0006 subjectsCompleted ≥2 consecutive treatment cycles, had ≥1 efficacy assessment \& no major protocol violations FG0017 subjectsCompleted ≥2 consecutive treatment cycles, had ≥1 efficacy assessment \& no major protocol violations FG0027 subjectsCompleted ≥2 consecutive treatment cycles, had ≥1 efficacy assessment \& no major protocol violations FG003
Completed 6 Cycles of Therapy		FG0004 subjects FG0012 subjects FG0021 subjects FG0030 subjects FG004
COMPLETED		FG0004 subjectsRepresents patients who completed the study through Cycle 6 FG0012 subjectsRepresents patients who completed the study through Cycle 6 FG0021 subjectsRepresents patients who completed the study through Cycle 6 FG003
NOT COMPLETED		FG0003 subjects FG0015 subjects FG0029 subjects FG0036 subjects FG004

Type	Comment	Reasons
Disease Progression		FG0003 subjects FG0013 subjects FG0023 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Dose Level 1	Participants received romidepsin 10 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1, 8, and 15 every 28 days.
BG001	Dose Level 2	Participants received romidepsin 7 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1, 8, and 15 every 28 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Safety population - all participants who received at least one dose of study drug.

Posted

Number

participants

28 days

ID	Title	Description
OG000	Dose Level 1	Participants received romidepsin 10 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1, 8, and 15 every 28 days.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dose Level 1	Participants received romidepsin 10 mg/m^2 plus gemcitabine 800 mg/m^2 on Days 1, 8, and 15 every 28 days.

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms

ID	Term
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D010455	Peptides

ID	Term
C087123	romidepsin
D047630	Depsipeptides
D000093542	Gemcitabine