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Combination Chemotherapy Plus Gene Therapy in Treating Patients With CNS Tumors

This study is ongoing, but not recruiting participants.

Sponsors and Collaborators: Indiana University Melvin and Bren Simon Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005796
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Inserting a specific gene into a person's peripheral stem cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus gene therapy in treating patients who have CNS tumors.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Cancer-Related Problem/Condition
Drug: filgrastim
Drug: lomustine
Drug: procarbazine hydrochloride
Drug: vincristine sulfate
Procedure: conventional surgery
Procedure: gene therapy
Procedure: in vitro-treated peripheral blood stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: radiation therapy
Phase I

MedlinePlus related topics:   Brain Cancer    Cancer    Childhood Brain Tumors   

Drug Information available for:   Filgrastim    Vincristine sulfate    Vincristine    Lomustine    Procarbazine hydrochloride    Procarbazine   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment
Official Title:   A Pilot Study of Dose-Intensified Procarbazine, CCNU, Vincristine (PCV) for Poor Prognosis Pediatric and Adult Brain Tumors Utilizing Fibronectin-Assisted, Retroviral-Mediated Modification of CD34+ Peripheral Blood Cells With O6-Methylguanine DNA Methyltransferase

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:   February 2000

Detailed Description:

OBJECTIVES: I. Determine the toxicity (detection of replication competent retrovirus) associated with CD34+ cells transduced with a retroviral vector expressing human O6-methylguanine DNA methyltransferase in adult and pediatric patients with poor prognosis CNS tumors. II. Determine the safety of genetic modification of cells carried out in the presence (ex vivo) of recombinant fibronectin (FN) fragment utilized to assist in retroviral entry into mammalian cells. III. Determine any evidence of engraftment of cells exposed to FN during retroviral transduction. IV. Determine any evidence of antibodies to FN following infusion of cells exposed to FN during ex vivo retroviral transduction.

OUTLINE: Patients with surgically approachable lesions undergo maximal surgical debulking that allows preservation of good neurologic functioning. Harvest: Patients receive filgrastim (G-CSF) subcutaneously or IV beginning 4 days prior to initiation of first leukapheresis and continuing until completion of harvest. Peripheral blood stem cells are harvested and selected for CD34+ cells which are transduced with a fibronectin assisted retroviral vector expressing human O6-methylguanine DNA methyltransferase. Intensification: Patients receive oral lomustine and vincristine IV on day 0 and oral procarbazine on days 1-7. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with newly diagnosed tumors may undergo involved field radiotherapy (IF-RT) after completion of the third course of chemotherapy and may begin the fourth course of chemotherapy after completion of IF-RT. Transplantation: Two-thirds of the transduced CD34+ cells are reinfused on day 9 of the first course of chemotherapy. The remaining portion (one-third) of the transduced CD34+ cells are reinfused on day 9 of the second course of chemotherapy. Untransduced CD34+ cells are reinfused on day 9 of the last 3 courses of chemotherapy. Patients are followed every 3 months for 6 months, every 4 months for 1 year, every 6 months through year 5, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 15-20 patients will be accrued for this study within 1 year.

  Eligibility
Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS: Histologically proven newly diagnosed CNS tumors Eligible tumor types: Glioblastoma multiforme (WHO grade IV) Anaplastic astrocytoma (WHO grade III) Anaplastic oligodendroglioma (WHO grade III) Mixed anaplastic oligoastrocytoma (WHO grade III) Incompletely resected ependymoma Diffusely intrinsic pontine or medullary glioma Histology requirement waived OR Histologically proven recurrent or progressive CNS tumors Eligible tumor types: Same as above plus oligodendroglioma (WHO grade II) No brainstem tumors arising from the cervicomedullary region or midbrain without histologic proof of malignancy No supratentorial low grade astrocytomas (WHO grade I or II)

PATIENT CHARACTERISTICS: Age: 5 and over Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 (transfusion independent) Hemoglobin greater than 10 g/dL at time of pulmonary function testing Hepatic: Bilirubin less than 1.2 mg/dL SGOT or SGPT less than 3 times normal Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance or radioisotope GFR greater than 70 mL/min Pulmonary: FEV1, FVC, and/or DLCO greater than 60% predicted Children who are uncooperative with pulmonary function tests must have the following: No evidence of dyspnea at rest No exercise intolerance Oxygen saturation (by pulse oximetry) greater than 94% on room air Other: Minimum weight of 10 kg Not pregnant or nursing No active infection

PRIOR CONCURRENT THERAPY: Biologic therapy: No growth factors after completion of study chemotherapy Chemotherapy: No prior nitrosourea or procarbazine Endocrine therapy: No concurrent dexamethasone as antiemetic Radiotherapy: No prior craniospinal radiotherapy Surgery: Not specified

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005796

Locations
United States, Indiana
Indiana University Cancer Center    
      Indianapolis, Indiana, United States, 46202-5265
United States, Massachusetts
Dana-Farber Cancer Institute    
      Boston, Massachusetts, United States, 02115

Sponsors and Collaborators
Indiana University Melvin and Bren Simon Cancer Center
National Cancer Institute (NCI)

Investigators
Study Chair:     James Croop, MD, PhD     Riley's Children Cancer Center at Riley Hospital for Children    
  More Information


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000067758, IUMC-9607-22, NCI-H00-0049
First Received:   June 2, 2000
Last Updated:   November 22, 2008
ClinicalTrials.gov Identifier:   NCT00005796
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult brain tumor  
adult brain stem glioma  
adult ependymoma  
adult medulloblastoma  
adult glioblastoma  
childhood high-grade cerebral astrocytoma  
childhood oligodendroglioma  
adult anaplastic astrocytoma  
adult anaplastic oligodendroglioma  
adult mixed glioma  
drug/agent toxicity by tissue/organ  
bone marrow suppression
untreated childhood brain stem glioma
recurrent childhood brain stem glioma
untreated childhood cerebellar astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
newly diagnosed childhood ependymoma
recurrent childhood ependymoma
adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Lomustine
Vincristine
Central Nervous System Neoplasms
Ependymoma
Recurrence
Brain Neoplasms
Medulloblastoma
Oligodendroglioma
Procarbazine
Glioma
Gliosarcoma
Nervous System Neoplasms

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Mitosis Modulators
Tubulin Modulators
Nervous System Diseases
Antimitotic Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on December 03, 2008




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