Melphalan With BBBD in Treating Patients With Brain Malignancies

NCT00253721 | Terminated Phase 1 DMC

• 5 other identifiers: IRB00001299P30CA0695331299ONC-98018-L4834
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors; Lymphoma; Metastatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)of Melphalan as measured by NCI common toxicity criteria (CTC) v2 toxicities

  MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects

  5 years

Secondary Outcomes (1)

• Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment

  5 years

Study Arms (1)

All subjects

EXPERIMENTAL

Drug: Melphalan

Interventions

Melphalan DRUG

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

All subjects

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Lymphoma; Neoplasm Metastasis; Astrocytoma; Medulloblastoma; Oligodendroglioma; Pinealoma; Brain Neoplasms; Glioma

Interventions

Melphalan

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Edward A. Neuwelt, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 11, 2005
• First Posted: November 15, 2005
• Study Start: May 1, 1998
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: April 21, 2017

Record last verified: 2017-04

Locations

US (1)