A Study Of Romidepsin (Depsipeptide) In Combination With Gemcitabine In Patients With Pancreatic And Other Advanced Solid Tumors

Study Overview

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.

N/A

Pancreatic Cancer

DRUG: Romidepsin
DRUG: Gemcitabine

GPI-06-0003

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-09-20	Results First Submitted 2012-07-05	Last Update Submitted that met QC Criteria 2019-10-16
First Submitted that Met QC Criteria 2006-09-20	Results First Submitted that Met QC Criteria 2012-07-05	Last Update Posted (ACTUAL) 2019-10-30
First Posted (ACTUAL) 2006-09-22	Results First Posted 2012-08-13	Last Verified 2019-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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 base	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. 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.

Participant Group/Arm

Intervention/Treatment

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 base

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.

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.

Primary Outcome Measures	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).

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

histologically confirmed advanced solid tumors
measurable or evaluable disease
written informed consent
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Howard A. Burris, M.D., SCRI Development Innovations, LLC

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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