Melphalan With BBBD in Treating Patients With Brain Malignancies

This study has suspended participant recruitment.
(suspended until revisions to study are completed)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00253721
First received: November 11, 2005
Last updated: October 25, 2013
Last verified: October 2013
  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 [Blood-Brain Barrier Disruption (BBBD)]and allow melphalan to be carried directly to the brain tumor. Giving melphalan together with BBBD 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
Lymphoma
Metastatic Cancer
Drug: Melphalan
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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 OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD)of Melphalan as measured by NCI CTC v2 toxicities [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects


Secondary Outcome Measures:
  • Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 1998
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects Drug: Melphalan

All levels: Every 4 weeks for up to one year

Dose Escalation Plan:

Level 1: 4mg/m2/day x 2 days

Level 2: 6mg/m2/day x 2 days

Level 3: 8mg/m2/day x 2 days

Level 4: 10mg/m2/day x 2 days

Level 5: 12mg/m2/day x 2 days


Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of intra-arterial melphalan when given in combination with BBBD in patients with primary or metastatic CNS malignancy.
  • Determine the toxic effects of melphalan given with BBBD 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 with BBBD followed by intra-arterial melphalan over 10 minutes on days 1 and 2*. Treatment repeats every 4 weeks for up to 12 monthly courses 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 every 3 months for 1 year; every 6 months for the next 2 years; then annually.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Signed written informed consent form in accordance with institutional guidelines
  • 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
  • Life expectancy at least 60 days
  • Radiographically evaluable disease by MRI or CT scan
  • Age 18 years or older
  • At least 28 days since prior radiotherapy (systemic, cranial, and/or spinal)
  • At least 28 days since prior chemotherapy (42 days for nitrosoureas)
  • Adequate cardiac and pulmonary function to tolerate general anesthesia
  • Performance status of ECOG 0-2
  • Other tumor masses in the spinal cord allowed provided there is no radiographic or clinical evidence of spinal cord block
  • Available for follow-up for at least one year following completion of treatment
  • Fertile patients must use effective contraception for 2 months prior to, during, and for 3 months after study participation
  • Pre-treatment lab tests within 14 days prior to initiation of treatment:

    • WBC > 2,500/mm^3
    • Absolute granulocyte count > 1,200/mm^3
    • Platelet count > 100,000/mm^3
    • Hematocrit > 30% (transfusion allowed)
    • Bilirubin ≤ 2 times upper limit of normal (ULN)
    • SGOT ≤ 3 times ULN
    • Creatinine ≤ 2 times ULN
  • Subjects with history of smoking or emphysema require DLCO ≥ 80% of predicted value for age
  • Histological sections submitted for pathology review

EXCLUSION CRITERIA:

  • Radiographic evidence of excessive intra-cranial mass effect and/or spinal block
  • Known hypersensitivity or intolerance to melphalan
  • NCI CTC Grade 3 or greater baseline neurologic symptoms
  • Immunologically compromised (Concurrent corticosteroids for tumor edema allowed)
  • Unable to tolerate general anesthesia
  • Pregnant, positive HCG test, or lactating
  • HIV positive
  • Receiving concurrent radiotherapy or immunotherapy
  • Serious illness that would preclude study participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00253721

Locations
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Edward A. Neuwelt, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00253721     History of Changes
Other Study ID Numbers: OHSU-1299, P30CA069533, 1299, ONC-98018-L, 4834
Study First Received: November 11, 2005
Last Updated: October 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by OHSU Knight Cancer Institute:
adult anaplastic astrocytoma
adult brain stem glioma
adult diffuse astrocytoma
adult central nervous system germ cell tumor
adult medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)
adult anaplastic oligodendroglioma
adult oligodendroglioma
adult pineoblastoma
tumors metastatic to brain
adult mixed glioma
recurrent adult brain tumor
primary central nervous system non-Hodgkin lymphoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Lymphoma
Neoplasm Metastasis
Nervous System Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplastic Processes
Nervous System Diseases
Pathologic Processes
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014