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

NCT ID: NCT00098761

Last Updated: 2011-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2008-02-29

Brief Summary

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.

Detailed Description

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent childhood brain stem glioma; recurrent childhood visual pathway and hypothalamic glioma; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; childhood central nervous system germ cell tumor; childhood choroid plexus tumor; childhood craniopharyngioma; childhood infratentorial ependymoma; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; childhood high-grade cerebral astrocytoma; childhood low-grade cerebral astrocytoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

laromustine

This is a dose escalation study. Participants receive 20, 30, 45, 60, 78, 103, 137, 182, or 242 mg/m2/day intravenously over 30 minutes for 5 consecutive days every 6 weeks up to 48 weeks.

Intervention Type: DRUG

Other Intervention Names

Cloretazine; VNP40101M

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Pediatric Brain Tumor Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Pediatric Brain Tumor Consortium

Principal Investigators

Sri Gururangan, MRCP (UK)

Role: STUDY_CHAIR

Duke University

Locations

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18281546 (View on PubMed)

Other Identifiers

PBTC-017

Identifier Type: -

Identifier Source: secondary_id

VION-VNP40101M

Identifier Type: -

Identifier Source: secondary_id

CDR0000396779

Identifier Type: -

Identifier Source: org_study_id