Brain and Central Nervous System TumorsPhase 1NCT00253721
Melphalan With BBBD in Treating Patients With Brain Malignancies
A Phase 1 study testing Melphalan in people with Brain and Central Nervous System Tumors and Lymphoma, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Lymphoma, Metastatic Cancer
- What is being tested?
- Melphalan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- May 1998to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 23Show fewer
- 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
Who cannot join
- 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
Show all 9Show fewer
- HIV positive
- Receiving concurrent radiotherapy or immunotherapy
- Serious illness that would preclude study participation
Trial locations and contacts
1 site in 1 country.
United States1 site
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, 97239-3098
About this study
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
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.
Read the 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.
- Being tested
- Melphalan
- 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
- Medical subject headings
- Central Nervous System Neoplasms, Lymphoma, Neoplasm Metastasis, Astrocytoma, Medulloblastoma, Oligodendroglioma, Pinealoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
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
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | Not described Receives: Drug: Melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Secondary outcomes (1)
Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2005 (estimated)
- Study startMay 1998
- Primary completionDec 2015
- Study completionDec 2016
Why it stopped: Other competing clinical trials affecting enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Edward Neuwelt, OHSU Knight Cancer Institute
- Investigators
- Edward A. Neuwelt, MD, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00253721
- Sponsor's protocol ID
- IRB00001299
- Other IDs
- P30CA069533, 1299, ONC-98018-L, 4834
- Status last verified
- Apr 2017
- First submitted
- 11 Nov 2005
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00253721
- Acronym / sponsor ID
- IRB00001299
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Other competing clinical trials affecting enrollment
- Enrolment
- 21 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 1998
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 15 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Drug: Melphalan |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelphalanAll 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 | Drug | All subjects |
Primary outcome
Maximum tolerated dose (MTD)of Melphalan as measured by NCI common toxicity criteria (CTC) v2 toxicities
Time frame: 5 years
MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects
1 secondary outcome
Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Other competing clinical trials affecting enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
Related trials for Brain and Central Nervous System Tumors
RecruitingPhase 2
A Study of Navlimetostat (BMS-986504) Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)
Solid Tumors
Active, not recruitingPhase 1/2
RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors
Recurrent Pulmonary Osteosarcoma, Recurrent High-grade Glioma
RecruitingObservational study
Activation Sarcoma: PROMIS and Mobility Evaluation in Sarcoma Patients
Sarcoma, Giant Cell Tumor of Bone
RecruitingEarly Phase 1
Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation
CNS Embryonal Tumor, CNS, Medulloblastoma
Recruiting
Buddy-Up Dyadic Physical Activity Program for Persons With Dementia and Family Caregivers
Cognitive Impairment, Mild, Dementia, Mild
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward A. Neuwelt, MD principal investigator
OHSU Knight Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Melphalan in people with Brain and Central Nervous System Tumors and Lymphoma, run by OHSU Knight Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Other competing clinical trials affecting enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD)of Melphalan as measured by NCI common toxicity criteria (CTC) v2 toxicities (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2017.