Melphalan With BBBD in Treating Patients With Brain Malignancies

OHSU Knight Cancer Institute

Status and phase

Terminated

Phase 1

Conditions

Metastatic Cancer

Brain and Central Nervous System Tumors

Lymphoma

Treatments

Drug: Melphalan

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00253721

IRB00001299

4834 (Other Identifier)

ONC-98018-L (Other Identifier)

1299

P30CA069533 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Determine the maximum tolerated dose of intra-arterial melphalan when given in combination with BBBD in patients with primary or metastatic central nervous system (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.

Enrollment

21 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

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 Eastern Cooperative Oncology Group (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:
- White blood cell count (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)
- Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times ULN
- Creatinine ≤ 2 times ULN
Subjects with history of smoking or emphysema require diffusing capacity of lung for carbon monoxide (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 human chorionic gonadotropin (HCG) test, or lactating
HIV positive
Receiving concurrent radiotherapy or immunotherapy
Serious illness that would preclude study participation