NCT00085540

Brief Summary

This phase I/II trial is studying the side effects and best dose of FR901228 and to see how well it works in treating patients with recurrent high-grade gliomas. FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2005

Longer than P75 for phase_1

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 10, 2004

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 11, 2004

Completed
7 months until next milestone

Study Start

First participant enrolled

January 1, 2005

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2008

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed
7.7 years until next milestone

Results Posted

Study results publicly available

November 15, 2016

Completed
Last Updated

January 2, 2017

Status Verified

November 1, 2016

Enrollment Period

3.9 years

First QC Date

June 10, 2004

Results QC Date

September 23, 2016

Last Update Submit

November 15, 2016

Conditions

Outcome Measures

Primary Outcomes (2)

  • Number of Participants With Dose-limiting Toxicities Due to Romidepsin Graded According to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I)

    dose limiting toxicity defined as: ANC \</=1000 or Platelets \<100K; SGOT \>/= 3X ULN and T. Bili \>/= 1.5 ULN grade 3 Nausea, vomiting, fatigue and asymptomatic hypocalcemia (treatment may continue after discuss with PI)

    First 4 weeks of treatment

  • 6 Months Progression-free Survival (Phase II)

    evaluated patients with glioblastoma (GBM (35 patients)

    At 6 months

Secondary Outcomes (1)

  • Response Rate Associated With Depsipeptide Therapy (Phase II)

    Up to 2 years

Study Arms (2)

Phase 1 Dose Escalation - Romidepsin

EXPERIMENTAL

Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dose escalation two dose levels: Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2 Pharmacokinetics

Drug: depsipeptide

Phase 2 Dose from Phase 1 - Romidepsin

EXPERIMENTAL

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Romidepsin (depsipeptide): 13.3mg/m2

Drug: depsipeptide

Interventions

Given IV

Also known as: FK228, FR901228, Istodax, romidepsin
Phase 1 Dose Escalation - RomidepsinPhase 2 Dose from Phase 1 - Romidepsin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Phase I and phase II:
  • Histologically confirmed recurrent intracranial malignant glioma, including any of the following:
  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Malignant astrocytoma not otherwise specified
  • Unequivocal evidence of tumor progression by MRI or CT scan while on a steroid dosage that has been stable for at least 5 days
  • Patients previously treated with interstitial brachytherapy or stereotactic radiosurgerymust have confirmation of true progressive disease (rather than radiation necrosis) by positron-emission tomography, thallium scan, magnetic resonance spectroscopy, or surgical documentation
  • Must have failed prior radiotherapy that was completed at least 6 weeks ago
  • No more than 2 prior therapies (initial treatment and treatment for 1 relapse)\*
  • Surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks, followed by a second surgical resection, is considered treatment for 1 relapse
  • Patients in group B must have been receiving enzyme-inducing antiepileptic drugs (EIAEDs) for at least the past 2 weeks
  • Performance status - Karnofsky 60-100%
  • +55 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

National Cancer Institute Neuro-Oncology Branch

Bethesda, Maryland, 20814, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

  • Iwamoto FM, Lamborn KR, Kuhn JG, Wen PY, Yung WK, Gilbert MR, Chang SM, Lieberman FS, Prados MD, Fine HA. A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03. Neuro Oncol. 2011 May;13(5):509-16. doi: 10.1093/neuonc/nor017. Epub 2011 Mar 3.

MeSH Terms

Conditions

AstrocytomaOligodendrogliomaGlioblastomaGliosarcomaBrain Neoplasms

Interventions

Depsipeptidesromidepsin

Condition Hierarchy (Ancestors)

GliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Peptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and Proteins

Limitations and Caveats

Dose escalation was terminated after 2 dose levels because PK parameters of romidepsin in pts receiving EIAEDs were similar to those reported in Adults not receiving CYP34A inducing drugs, we wanted to avoid the expected dose limiting toxicity.

Results Point of Contact

Title
Howard Fine, MD
Organization
Adult Brain Tumor Consortium (ABTC)

Study Officials

  • Howard Fine, MD

    North American Brain Tumor Consortium

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

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

Study Record Dates

First Submitted

June 10, 2004

First Posted

June 11, 2004

Study Start

January 1, 2005

Primary Completion

December 1, 2008

Study Completion

March 1, 2009

Last Updated

January 2, 2017

Results First Posted

November 15, 2016

Record last verified: 2016-11

Data Sharing

IPD Sharing
Will not share

Locations