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

29 giugno 2011 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Tumori cerebrali e del sistema nervoso centrale

Intervento / Trattamento

Droga: laromustine

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

Fase

Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Non più vecchio di 21 anni (Bambino, Adulto)

Accetta volontari sani

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Scopo principale: Trattamento
Assegnazione: N / A
Modello interventistico: Assegnazione di gruppo singolo
Mascheramento: Nessuno (etichetta aperta)

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato	Lasso di tempo
Estimate the maximum tolerated dose Lasso di tempo: First 6 weeks of therapy	First 6 weeks of therapy
Number of participants with dose limiting toxicities Lasso di tempo: First 6 weeks of therapy	First 6 weeks of therapy

Misure di risultato secondarie

Misura del risultato	Misura Descrizione	Lasso di tempo
Pharmacokinetics Lasso di tempo: 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 Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Pediatric Brain Tumor Consortium

Collaboratori

National Cancer Institute (NCI)

Investigatori

Cattedra di studio: Sri Gururangan, MRCP (UK), Duke University

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

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.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 febbraio 2005

Completamento primario (Effettivo)

1 ottobre 2006

Completamento dello studio (Effettivo)

1 febbraio 2008

Date di iscrizione allo studio

Primo inviato

8 dicembre 2004

Primo inviato che soddisfa i criteri di controllo qualità