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Adult Anaplastic AstrocytomaPhase 1/2NCT00085540

FR901228 in Treating Patients With Recurrent High-Grade Gliomas

A Phase 1/2 study testing depsipeptide in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
depsipeptide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
8 sitesUnited States
Study dates
Jan 2005to Mar 2009
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phase I and phase II:
  • Histologically confirmed recurrent intracranial malignant glioma, including any of the following:
  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
Show all 70Show fewer
  • 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%
  • More than 8 weeks
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusions allowed)
  • SGOT < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • Creatinine < 1.5 mg/dL
  • No congestive heart failure (i.e., New York Heart Association class II-IV, ejection fraction < 40% by MUGA scan or < 50% by echocardiogram and/or MRI)
  • No myocardial infarction within the past year
  • No uncontrolled dysrhythmias
  • No poorly controlled angina
  • No significant left ventricular hypertrophy by EKG
  • No cardiac ischemia (ST depression of 2 mm) by EKG
  • No hypertrophic or restrictive cardiomyopathy from prior treatment or other causes
  • No uncontrolled hypertension (i.e., blood pressure ≥ 160/95 mm Hg)
  • No cardiac arrhythmia requiring antiarrhythmic medication
  • No known cardiac abnormalities (e.g., congenital long QT syndrome and QTc interval > 480 milliseconds)
  • No history of sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, or cardiac arrest unless controlled with concurrent automatic implantable cardioverter defibrillator
  • No known history of coronary artery disease (e.g., Canadian class II-IV angina)
  • No other significant cardiac disease
  • No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No active infection
  • No significant uncontrolled medical illness that would preclude study participation
  • No disease that would obscure toxicity or dangerously alter drug metabolism
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 2 weeks after study participation
  • Fertile male patients must continue barrier contraception for 3 months after study participation
  • At least 1 week since prior interferon or thalidomide
  • No concurrent prophylactic filgrastim (G-CSF)
  • No concurrent anticancer immunotherapy
  • At least 2 weeks since prior vincristine
  • At least 6 weeks since prior nitrosoureas
  • At least 3 weeks since prior procarbazine
  • No prior FR901228 (depsipeptide)
  • No other concurrent anticancer chemotherapy
  • See Disease Characteristics
  • At least 1 week since prior tamoxifen
  • No concurrent anticancer hormonal therapy
  • See Disease Characteristics
  • No concurrent anticancer radiotherapy
  • See Disease Characteristics
  • Prior recent resection of recurrent or progressive tumor allowed if patient has recovered
  • Recovered from all prior therapy
  • At least 2 weeks since prior EIAEDs (patients in Group A only)
  • At least 4 weeks since prior cytotoxic therapy
  • At least 4 weeks since prior investigational agents
  • At least 1 week since prior isotretinoin
  • At least 1 week since other prior non-cytotoxic therapy (except radiosensitizers)
  • No concurrent valproic acid
  • No concurrent hydrochlorothiazide
  • No concurrent medication that causes QTc prolongation
  • No other concurrent anticancer therapy
  • No other concurrent investigational drugs

Who cannot join

None listed.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • National Cancer Institute Neuro-Oncology Branch

    Bethesda, Maryland, 20814

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Los Angeles

    Los Angeles, California, 90095

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) of FR901228 (depsipeptide) in patients with recurrent malignant gliomas who are taking enzyme-inducing antiepileptic drugs (EIAEDs). (Phase I) II. Determine the safety profile of this drug in these patients. (Phase I) III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. (Phase I) IV. Determine the clinical efficacy of this drug, as measured by 6-month progression-free survival and objective tumor response, in these patients. (Phase II) V. Determine the safety profile of this drug when administered at the phase I MTD concurrently with or without EIAEDs in these patients. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study. Patients are stratified according to study phase (I vs II), concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) (yes vs no), histology (recurrent glioblastoma multiforme/gliosarcoma vs recurrent anaplastic glioma), pre-operative candidacy (yes vs no), and measurable/evaluable disease (yes vs no). Patients are assigned to 1 of 2 treatment groups (group A: no EIAEDs or group B: concurrent use of EIAEDs).

Phase I (group B only): Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose-limiting toxicity.

Phase II (groups A and B):

Group A (phase II): Patients receive FR901228 as in phase I at dose level 1. Group B (phase II): Patients receive FR901228 as in phase I at the MTD.

Being tested
depsipeptide
Medical subject headings
Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • depsipeptideDrug

    Also called FK228, FR901228, Istodax, romidepsin

    Given IV

Study groups in NCT00085540
Study groupRoleWhat they receive
Phase 1 Dose Escalation - RomidepsinExperimentalPatients 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
Receives: Drug: depsipeptide
Phase 2 Dose from Phase 1 - RomidepsinExperimentalPatients 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
Receives: Drug: depsipeptide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: First 4 weeks of treatment

  2. 6 Months Progression-free Survival (Phase II)

    evaluated patients with glioblastoma (GBM (35 patients)

    Measured: At 6 months

Secondary outcomes (1)

  1. Response Rate Associated With Depsipeptide Therapy (Phase II)

    RECIST Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients must be on no steroids.

    Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.

    Stable/No Response: Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration.

    Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2004 (estimated)
  2. Study startJan 2005
  3. Primary completionDec 2008
  4. Study completionMar 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00085540
Sponsor's protocol ID
NCI-2012-02596
Other IDs
NABTC-0303, U01CA062399, CDR0000370817
Status last verified
Nov 2016
First submitted
10 Jun 2004
Last updated
2 Jan 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 21377994

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing depsipeptide in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 70 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicities Due to Romidepsin Graded According to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I) (time frame: First 4 weeks of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00085540, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2017.

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