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Melphalan and Mannitol in Treating Patients With Central Nervous System Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: November 11, 2005   Last Updated: June 9, 2009   History of Changes
Sponsors and Collaborators: Oregon Health and Science University
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00253721
  Purpose

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving drugs directly into the arteries around the tumor may kill more tumor cells. Mannitol may open the blood vessels around the brain and allow melphalan to be carried directly to the brain. Giving melphalan together with mannitol may be an effective treatment for central nervous system cancer.

PURPOSE: This phase I trial is studying side effects and best dose of melphalan when given together with mannitol in treating patients with central nervous system cancer.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Chordoma
Lymphoma
Von Hippel-Lindau Syndrome
Drug: mannitol
Drug: melphalan
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: Intra-Arterial Melphalan (L-Phenylalanine Mustard) Administered in Conjunction With Osmotic Blood-Brain Barrier Disruption in Patients With Brain Malignancies: A Phase I Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose as measured by NCI CTC v2 toxicities [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy of chemotherapy regimen as measured by clinical and radiographic response continuously from first day of treatment [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 1998
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of intra-arterial melphalan when given in combination with mannitol in patients with primary or metastatic CNS malignancy.
  • Determine the toxic effects of this regimen in these patients.
  • Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of melphalan.

Patients receive intra-arterial mannitol followed by melphalan over 10 minutes on days 1 and 2*. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients with gliomas localized to the posterior circulation (i.e., brain stem gliomas) receive melphalan on day 1 only.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study therapy, patients are followed periodically for at least 1 year.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary or metastatic CNS malignancy

    • Patients with metastatic disease must have histological confirmation of the primary cancer AND confirmation by surgical specimen, cerebrospinal fluid cytology, elevated tumor markers, or clinical evidence of CNS involvement
  • Single or multiple cerebellar or cerebral cortex lesions allowed
  • Radiographically evaluable disease by MRI or CT scan
  • Other tumor masses in the spinal cord allowed provided there is no radiographic or clinical evidence of spinal cord block
  • No radiographic evidence of uncal herniation

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • At least 60 days

Hematopoietic

  • WBC > 2,500/mm^3
  • Absolute granulocyte count > 1,200/mm^3
  • Platelet count > 100,000/mm^3
  • Hematocrit > 30% (transfusion allowed)

Hepatic

  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • SGOT ≤ 3 times ULN

Renal

  • Creatinine ≤ 2 times ULN

Cardiovascular

  • Adequate cardiac function

Pulmonary

  • Adequate pulmonary function
  • DLCO ≥ 80% of predicted for patients with prior smoking history or emphysema

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 2 months prior to*, during, and for 3 months after study participation
  • Able to tolerate general anesthesia
  • No known hypersensitivity or intolerance to melphalan
  • No grade 3 or greater baseline neurologic symptoms
  • Not immunologically compromised
  • No known HIV positivity
  • No other serious illness that would preclude study participation [Note: *This criterion may be waived at the discretion of the investigator for patients with life-threatening tumors for which the 2-month wait would not be feasible]

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy

Chemotherapy

  • At least 28 days since prior chemotherapy (42 days for nitrosoureas)

Endocrine therapy

  • Concurrent corticosteroids for tumor edema allowed

Radiotherapy

  • At least 28 days since prior radiotherapy (systemic, cranial, and/or spinal)
  • No concurrent radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00253721

Locations
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea     503-494-1080     trials@ohsu.edu    
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Edward A. Neuwelt, MD Oregon Health and Science University
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000445051, OHSU-1299, OHSU-ONC-98018-L, OHSU-4834
Study First Received: November 11, 2005
Last Updated: June 9, 2009
ClinicalTrials.gov Identifier: NCT00253721     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
adult anaplastic astrocytoma
adult brain stem glioma
adult diffuse astrocytoma
adult giant cell glioblastoma
adult gliosarcoma
adult central nervous system germ cell tumor
adult choroid plexus tumor
adult craniopharyngioma
adult ependymoblastoma
adult medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)
adult anaplastic ependymoma
adult ependymoma
adult myxopapillary ependymoma
adult subependymoma
adult anaplastic meningioma
adult melanocytic lesion
adult meningeal hemangiopericytoma
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult anaplastic oligodendroglioma
adult oligodendroglioma
adult pineoblastoma
adult pineocytoma
adult pilocytic astrocytoma
adult papillary meningioma
adult tumors metastatic to brain
adult mixed glioma
childhood mixed glioma

Study placed in the following topic categories:
Melphalan
Glioblastoma
Choroid Plexus Neoplasms
Neuroectodermal Tumors, Primitive
Angiomatosis
Immunologic Factors
Diuretics
Central Nervous System Lymphoma, Primary
Central Nervous System Neoplasms
Phenylalanine
Chordoma
Ependymoma
Von Hippel-Lindau Disease
Mannitol
Neoplasms, Germ Cell and Embryonal
Craniopharyngioma
Neuroepithelioma
Meningioma
Glioma
Alkylating Agents
Lymphoma
Nervous System Neoplasms
Neurocutaneous Syndromes
Immunoproliferative Disorders
Von Hippel-Lindau Syndrome
Astrocytoma
Vascular Diseases
Cardiovascular Agents
Immunosuppressive Agents
Hemangiopericytoma

Additional relevant MeSH terms:
Melphalan
Angiomatosis
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Diuretics
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Chordoma
Neoplasms by Site
Pathologic Processes
Von Hippel-Lindau Disease
Mannitol
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Syndrome
Cardiovascular Diseases
Glioma
Alkylating Agents
Lymphoma
Nervous System Neoplasms
Neurocutaneous Syndromes
Neoplasms by Histologic Type
Immunoproliferative Disorders
Disease
Astrocytoma
Immune System Diseases
Diuretics, Osmotic
Nervous System Diseases

ClinicalTrials.gov processed this record on July 06, 2009