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

NCT00098761 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000396779PBTC-017VION-VNP40101M
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 10

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.

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

Outcome Measures

Primary Outcomes (2)

• Estimate the maximum tolerated dose

  First 6 weeks of therapy

• Number of participants with dose limiting toxicities

  First 6 weeks of therapy

Secondary Outcomes (2)

• Pharmacokinetics

  Day 1 of therapy

• Tumor response to VNP40101M

  Prior to course 3, 5, and 7 and end of therapy

Interventions

laromustine DRUG

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.

Also known as: Cloretazine, VNP40101M

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

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

Houston, Texas, 77030-2399, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• 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.

  PMID: 18281546 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Optic Nerve Glioma; Astrocytoma; Familial ependymoma; Medulloblastoma; Choroid Plexus Neoplasms

Interventions

laromustine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Neuroectodermal Tumors, Primitive; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases

Study Officials

• Sri Gururangan, MRCP (UK)

  Duke University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: December 8, 2004
• First Posted: December 9, 2004
• Study Start: February 1, 2005
• Primary Completion: October 1, 2006
• Study Completion: February 1, 2008
• Last Updated: June 30, 2011

Record last verified: 2011-06

Locations

US (10)