Melphalan With BBBD in Treating Patients With Brain Malignancies - Full Text View

Sponsor:	OHSU Knight Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	OHSU Knight Cancer Institute
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 [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 I

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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

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 2012 (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

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

Contacts

Contact: Edward A Neuwelt, MD	503-494-5626	neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA	503-494-5626	hedrickn@ohsu.edu

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
Principal Investigator: Edward A Neuwelt, MD

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Edward A. Neuwelt, MD

OHSU Knight Cancer Institute

More Information

Additional Information:

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

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:	September 22, 2011
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:

Lymphoma
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes

Neoplasms by Site
Nervous System Diseases
Melphalan
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 13, 2012