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FR901228 in Treating Patients With Recurrent High-Grade Gliomas

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ClinicalTrials.gov Identifier: NCT00085540
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : November 15, 2016
Last Update Posted : January 2, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE June 10, 2004
First Posted Date  ICMJE June 11, 2004
Results First Submitted Date  ICMJE September 23, 2016
Results First Posted Date  ICMJE November 15, 2016
Last Update Posted Date January 2, 2017
Study Start Date  ICMJE January 2005
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2016)
  • 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 ]
    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)
  • 6 Months Progression-free Survival (Phase II) [ Time Frame: At 6 months ]
    evaluated patients with glioblastoma (GBM (35 patients)
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00085540 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2016)
Response Rate Associated With Depsipeptide Therapy (Phase II) [ Time Frame: Up to 2 years ]
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
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FR901228 in Treating Patients With Recurrent High-Grade Gliomas
Official Title  ICMJE A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas
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
Detailed Description

PRIMARY OBJECTIVES:

I. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Anaplastic Astrocytoma
  • Adult Anaplastic Oligodendroglioma
  • Adult Giant Cell Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
Intervention  ICMJE Drug: depsipeptide
Given IV
Other Names:
  • FK228
  • FR901228
  • Istodax
  • romidepsin
Study Arms  ICMJE
  • Experimental: Phase 1 Dose Escalation - Romidepsin

    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

    Intervention: Drug: depsipeptide
  • Experimental: Phase 2 Dose from Phase 1 - Romidepsin

    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

    Intervention: Drug: depsipeptide
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 23, 2016)
50
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2009
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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%
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00085540
Other Study ID Numbers  ICMJE NCI-2012-02596
NABTC-0303
U01CA062399 ( U.S. NIH Grant/Contract )
CDR0000370817 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Howard Fine, MD North American Brain Tumor Consortium
PRS Account National Cancer Institute (NCI)
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP