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

NCT00379639 | Completed Phase 1 Results

• 1 other identifier: GPI-06-0003
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

Pancreatic cancer; advanced solid tumors

Outcome Measures

Primary Outcomes (3)

• 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).

Study Arms (1)

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

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.

Also known as: ISTODAX®, Depsipeptide, FK228

Romidepsin / Gemcitabine

Gemcitabine DRUG

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.

Also known as: Gemzar®

Romidepsin / Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• 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.

  PMID: 22536933 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

romidepsin; Depsipeptides; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Howard A. Burris, M.D.

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2006
• First Posted: September 22, 2006
• Study Start: July 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: October 30, 2019
• Results First Posted: August 13, 2012

Record last verified: 2019-10

Locations

US (1)