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VNP40101M in Treating Young Patients With Recurrent, Progressive, or Refractory Primary Brain Tumors

29. juni 2011 opdateret af: Pediatric Brain Tumor Consortium

Phase I Study Of Cloretazine (VNP40101M) In Children With Recurrent, Progressive Or Refractory Primary Brain Tumors

RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of VNP40101M in treating young patients with recurrent, progressive, or refractory primary brain tumors.

Studieoversigt

Status

Afsluttet

Betingelser

Tumorer i hjernen og centralnervesystemet

Intervention / Behandling

Medicin: laromustine

Detaljeret beskrivelse

OBJECTIVES:

Primary

Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.

Secondary

Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
Determine the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to receiving ≥ 1 of the following prior therapies: craniospinal irradiation (yes vs no), autologous bone marrow transplant (yes vs no), and > 2 myelosuppressive chemotherapy or myelosuppressive biologic therapy regimens (yes vs no).

Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 months.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

Fase

Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

Forenede Stater
- California
  - San Francisco, California, Forenede Stater, 94115
    - UCSF Comprehensive Cancer Center
- District of Columbia
  - Washington, District of Columbia, Forenede Stater, 20010-2970
    - Children's National Medical Center
- Illinois
  - Chicago, Illinois, Forenede Stater, 60614
    - Children's Memorial Hospital - Chicago
- Massachusetts
  - Boston, Massachusetts, Forenede Stater, 02115
    - Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
- North Carolina
  - Durham, North Carolina, Forenede Stater, 27710
    - Duke Comprehensive Cancer Center
- Pennsylvania
  - Philadelphia, Pennsylvania, Forenede Stater, 19104-4318
    - Children's Hospital of Philadelphia
  - Pittsburgh, Pennsylvania, Forenede Stater, 15213
    - Children's Hospital of Pittsburgh
- Tennessee
  - Memphis, Tennessee, Forenede Stater, 38105
    - St. Jude Children's Research Hospital
- Texas
  - Houston, Texas, Forenede Stater, 77030-2399
    - Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
- Washington
  - Seattle, Washington, Forenede Stater, 98105
    - Children's Hospital and Regional Medical Center - Seattle

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

Ikke ældre end 21 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

Histologically confirmed* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)
- Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression
No bone marrow disease

PATIENT CHARACTERISTICS:

Age

21 and under

Performance status

Karnofsky 50-100% (for patients > 16 years of age) OR
Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,000/mm^3*
Platelet count ≥ 100,000/mm^3*
Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT and AST ≤ 2.5 times ULN
No overt hepatic disease

Renal

BUN < 25 mg/dL
Creatinine ≤ 1.5 times ULN for age OR
Glomerular filtration rate > 70 mL/min
No overt renal disease

Cardiovascular

Shortening fraction ≥ 30% by echocardiogram OR
Ejection fraction ≥ 50% by gated radionucleotide study
No clinically significant cardiac arrhythmia by EKG
No overt cardiac disease

Pulmonary

DLCO ≥ 60% of predicted
Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrhage, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
No overt pulmonary disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
No uncontrolled infection
No known hypersensitivity to polyethylene glycol

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 6 months since prior allogeneic bone marrow or stem cell transplantation
At least 3 months since prior autologous bone marrow or stem cell transplantation
More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
At least 3 weeks since prior myelosuppressive anticancer biologic therapy
No concurrent routine colony-stimulating factors

Chemotherapy

At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry

Radiotherapy

At least 3 months since prior craniospinal irradiation ≥ 18 Gy
At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites

Surgery

Not specified

Other

At least 7 days since prior nonmyelosuppressive anticancer therapy
At least 7 days since prior investigational agents
Concurrent enzyme-inducing anticonvulsant drugs allowed
No other concurrent anticancer or experimental agents or therapies

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Primært formål: Behandling
Tildeling: N/A
Interventionel model: Enkelt gruppeopgave
Maskning: Ingen (Åben etiket)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål	Tidsramme
Estimate the maximum tolerated dose Tidsramme: First 6 weeks of therapy	First 6 weeks of therapy
Number of participants with dose limiting toxicities Tidsramme: First 6 weeks of therapy	First 6 weeks of therapy

Sekundære resultatmål

Resultatmål	Foranstaltningsbeskrivelse	Tidsramme
Pharmacokinetics Tidsramme: Day 1 of therapy	Plasma samples for pharmacokinetic studies will be collected with the first dose of the study drug pre-infusion, and 5, 15, and 30 minutes, 1 hour, 2 hours, and 4 hours after the end of infusion. VNP40101M plasma concentration-time data will be modeled and the individual pharmacokinetic pararmeters volume of the central compartment, elimination rate constant, and half-life will be estimated.	Day 1 of therapy
Tumor response to VNP40101M Tidsramme: Prior to course 3, 5, and 7 and end of therapy	MRI of the brain will be obtained prior to couses 3, 5, and 7 and at the end of therapy	Prior to course 3, 5, and 7 and end of therapy

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Pediatric Brain Tumor Consortium

Samarbejdspartnere

National Cancer Institute (NCI)

Efterforskere

Studiestol: Sri Gururangan, MRCP (UK), Duke University

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Gururangan S, Turner CD, Stewart CF, O'Shaughnessy M, Kocak M, Poussaint TY, Phillips PC, Goldman S, Packer R, Pollack IF, Blaney SM, Karsten V, Gerson SL, Boyett JM, Friedman HS, Kun LE. Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study. Clin Cancer Res. 2008 Feb 15;14(4):1124-30. doi: 10.1158/1078-0432.CCR-07-4242.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. februar 2005

Primær færdiggørelse (Faktiske)

1. oktober 2006

Studieafslutning (Faktiske)

1. februar 2008

Datoer for studieregistrering

Først indsendt

8. december 2004

Først indsendt, der opfyldte QC-kriterier