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Melphalan With BBBD in Treating Patients With Brain Malignancies

Primary Purpose

Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Melphalan
Sponsored by
OHSU Knight Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Knight Cancer Institute at Oregon Health and Science University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All subjects

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
November 11, 2005
Last Updated
April 19, 2017
Sponsor
OHSU Knight Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00253721
Brief Title
Melphalan With BBBD in Treating Patients With Brain Malignancies
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
Other competing clinical trials affecting enrollment
Study Start Date
May 1998 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
OHSU Knight Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
All subjects
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)of Melphalan as measured by NCI common toxicity criteria (CTC) v2 toxicities
Description
MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward A. Neuwelt, MD
Organizational Affiliation
OHSU Knight Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Knight Cancer Institute at Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States

12. IPD Sharing Statement

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Melphalan With BBBD in Treating Patients With Brain Malignancies

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