Brain and Central Nervous System TumorsPhase 2NCT00445965
Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer
A Phase 2 study testing DNA analysis, immunologic technique and pharmacological study in people with Brain and Central Nervous System Tumors and Intraocular Melanoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Brain and Central Nervous System Tumors, Intraocular Melanoma, Lung Cancer
- What is being tested?
- DNA analysis, immunologic technique and pharmacological study
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to 1 Feb 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a histologically confirmed diagnosis of a malignancy known to expressGD2. Such tumors include medulloblastoma/primitive neuroectodermal tumor of the CNS, high grade astrocytomas, malignant glioma, neuroblastoma, retinoblastoma, ependymoma, rhabdoid tumors, sarcomas, melanoma or small cell lung carcinoma. For patients with other tumor types, GD2 expression must be confirmed by immunohistochemical staining and assessed by the Department of Pathology using prior frozen tissue, bone marrow or CSF cytology (send to Research Lab).
- Patients must have CNS/ leptomeningeal disease including high risk medulloblastoma, or a CNS/leptomeningeal malignancy which is refractory to conventional therapies, or for which no conventional therapy exists, OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, PNET, rhabdoid tumor).
- Patients must have an absolute neutrophil count (ANC) > 1000/ul and a platelet count > 50,000/ul.
- Patients may have active malignancy outside the central nervous system.
- Patients who have a programmable shunt will not be excluded.
- Both pediatric and adult patients of any age are eligible.
- Patients or a legal guardian will sign an informed consent form approved by the IRB and obtained by the Principal or a Co- Investigator before patient entry. Minors will provide assent.
Who cannot join
- Patients with obstructive or symptomatic communicating hydrocephalus.
- Patients with an uncontrolled life-threatening infection.
- Patients who are pregnant: Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is required during the study period.
- Patients who have received cranial or spinal irradiation less than 3 weeks prior to the start of this protocol.
- Patients who have received systemic chemotherapy (corticosteroids not included) less than 3 weeks prior to the start of this protocol.
- Severe major organ toxicity. Specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than or equal to grade 2. Patients with stable neurological deficits (because of their brain tumor) are not excluded. Patients with <= 3 hearing loss are not excluded.
- Patients must have no rapidly progressing or deteriorating neurologic examination.
- Patients who have already received >45 Gy to the craniospinal radiation or >72 Gy focal brain radiation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases.
PURPOSE: This phase II trial is studying the side effects and how well iodine I 131 monoclonal antibody 3F8 works in treating patients with central nervous system cancer or leptomeningeal cancer.
Read the detailed description
OBJECTIVES:
- Determine if intrathecal iodine I 131 monoclonal antibody 3F8 activity in patients with GD2-expressing central nervous system or leptomeningeal neoplasms is sufficiently promising (i.e., 6-month overall survival rate ≥ 25%) to warrant further study.
- Determine the response rate in patients treated with this drug.
- Determine the cumulative toxicities of this drug in these patients.
- Describe the effects of human-antimouse antibody on cerebrospinal fluid and serum pharmacokinetics in patients treated with this drug.
OUTLINE: This is an open-label study.
Patients receive intrathecal iodine I 131 monoclonal antibody 3F8 for dosimetry. Beginning approximately 1 week later, patients receive intrathecal iodine I 131 monoclonal antibody 3F8 on day 1. Treatment intrathecal iodine I 131 monoclonal antibody 3F8 repeats weekly for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Blood and cerebrospinal fluid samples are collected prior to and after administration of each course of study drug. Samples are analyzed to assess the intrathecal and blood pharmacokinetics of iodine I 131 monoclonal antibody 3F8 and serum human antimouse antibodies. Samples are also analyzed in tumor genetic studies.
After completion of study treatment, patients are followed periodically for 3 months.
- Conditions
- Brain and Central Nervous System Tumors, Intraocular Melanoma, Lung Cancer, Melanoma (Skin), Metastatic Cancer, Neuroblastoma
- Being tested
- DNA analysis, immunologic technique, pharmacological study, iodine I 131 monoclonal antibody 3F8, 131I-3F8
- Keywords
- recurrent childhood medulloblastoma, untreated childhood medulloblastoma, adult supratentorial primitive neuroectodermal tumor (PNET), recurrent childhood supratentorial primitive neuroectodermal tumor, untreated childhood supratentorial primitive neuroectodermal tumor, adult anaplastic astrocytoma, adult diffuse astrocytoma, adult pilocytic astrocytoma, adult subependymal giant cell astrocytoma, recurrent childhood subependymal giant cell astrocytoma, untreated childhood subependymal giant cell astrocytoma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, untreated childhood cerebellar astrocytoma, adult brain stem glioma, adult mixed glioma, childhood mixed glioma, recurrent childhood brain stem glioma, recurrent childhood visual pathway and hypothalamic glioma, recurrent childhood visual pathway glioma
- Medical subject headings
- Central Nervous System Neoplasms, Uveal Melanoma, Lung Neoplasms, Melanoma, Neoplasm Metastasis, Neuroblastoma, Ovarian Neoplasms, Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA analysisGenetic
immunologic techniqueOther
iodine I 131 monoclonal antibody 3F8Radiation
131I-3F8Radiation
Patients will receive 10mCi intrathecal 131I-3F8 per week. Patients will be pre-medicated with dexamethasone to prevent possible meningeal inflammatory reaction, Liothyronine and SSKI to prevent thyroid accumulation, and acetaminophen and diphenhydramine in anticipation of possible allergic reaction and fever.
| Study group | Role | What they receive |
|---|---|---|
| 131I-3F8 | Experimental | This is a phase II single-arm open-label study that will define responses to therapy with weekly intrathecal 131I-3F8 in patients with central nervous system/leptomeningeal GD2-expressing disease. Receives: Genetic: DNA analysis; Other: immunologic technique; Other: pharmacological study; Radiation: iodine I 131 monoclonal antibody 3F8; Radiation: 131I-3F8 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-month Overall Survival
Measured: 6 months
Number of Participants With Response at 6 Months
Complete Response (CR): Cytologic and radiographic CR will be evaluated separately, since patients with cytologic clearing and clinical response may continue to have residual abnormalities on MRI scans. Patients with a CR must also have stable or improved neurologic exam.
Stable Disease (SD): Exists when a patient fails to fulfill the criteria for either complete or partial response or progressive disease.
Progressive Disease (PD): An increase of at least 50% in the absolute number of malignant cells in the CSF OR, in -solid tumor patients, an increase of greater than 25% in the size of measurable lesions on MR scan OR the recurrence of malignant cells in the CSF or new lesions on MR after a patient has attained a complete remission OR evidence of clinical neurologic progression. New sites of or increasing evidence of leptomeningeal enhancement that is not "measurable" will also be considered evidence of disease progression.
Measured: 6 months
Secondary outcomes (1)
Number of Participants Evaluable for Toxicities
Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2007 (estimated)
- Study startJan 2006
- Primary completion1 Feb 2023
- Study completion1 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kim Kramer, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00445965
- Sponsor's protocol ID
- 05-122
- Other IDs
- MSKCC-05122
- Status last verified
- Feb 2023
- First submitted
- 7 Mar 2007
- Last updated
- 4 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms
- ClinicalTrials.gov ID
- NCT00445965
- Acronym / sponsor ID
- 05-122
- Conditions
- Brain and Central Nervous System Tumors, Intraocular Melanoma, Lung Cancer, Melanoma (Skin), Metastatic Cancer, Neuroblastoma
- Keywords
- recurrent childhood medulloblastoma, untreated childhood medulloblastoma, adult supratentorial primitive neuroectodermal tumor (PNET), recurrent childhood supratentorial primitive neuroectodermal tumor, untreated childhood supratentorial primitive neuroectodermal tumor, adult anaplastic astrocytoma, adult diffuse astrocytoma, adult pilocytic astrocytoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- Jan 2006 (actual)
- Primary completion
- 1 Feb 2023 (actual)
- Study completion
- 1 Feb 2023 (actual)
- First posted
- 9 Mar 2007 (estimated)
- Results
- Posted 4 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases.
PURPOSE: This phase II trial is studying the side effects and how well iodine I 131 monoclonal antibody 3F8 works in treating patients with central nervous system cancer or leptomeningeal cancer.
Detailed description
OBJECTIVES:
- Determine if intrathecal iodine I 131 monoclonal antibody 3F8 activity in patients with GD2-expressing central nervous system or leptomeningeal neoplasms is sufficiently promising (i.e., 6-month overall survival rate ≥ 25%) to warrant further study.
- Determine the response rate in patients treated with this drug.
- Determine the cumulative toxicities of this drug in these patients.
- Describe the effects of human-antimouse antibody on cerebrospinal fluid and serum pharmacokinetics in patients treated with this drug.
OUTLINE: This is an open-label study.
Patients receive intrathecal iodine I 131 monoclonal antibody 3F8 for dosimetry. Beginning approximately 1 week later, patients receive intrathecal iodine I 131 monoclonal antibody 3F8 on day 1. Treatment intrathecal iodine I 131 monoclonal antibody 3F8 repeats weekly for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Blood and cerebrospinal fluid samples are collected prior to and after administration of each course of study drug. Samples are analyzed to assess the intrathecal and blood pharmacokinetics of iodine I 131 monoclonal antibody 3F8 and serum human antimouse antibodies. Samples are also analyzed in tumor genetic studies.
After completion of study treatment, patients are followed periodically for 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 131I-3F8 | Experimental | Genetic: DNA analysis, Other: immunologic technique, Other: pharmacological study, Radiation: iodine I 131 monoclonal antibody 3F8, Radiation: 131I-3F8This is a phase II single-arm open-label study that will define responses to therapy with weekly intrathecal 131I-3F8 in patients with central nervous system/leptomeningeal GD2-expressing disease. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have a histologically confirmed diagnosis of a malignancy known to expressGD2. Such tumors include medulloblastoma/primitive neuroectodermal tumor of the CNS, high grade astrocytomas, malignant glioma, neuroblastoma, retinoblastoma, ependymoma, rhabdoid tumors, sarcomas, melanoma or small cell lung carcinoma. For patients with other tumor types, GD2 expression must be confirmed by immunohistochemical staining and assessed by the Department of Pathology using prior frozen tissue, bone marrow or CSF cytology (send to Research Lab).
- Patients must have CNS/ leptomeningeal disease including high risk medulloblastoma, or a CNS/leptomeningeal malignancy which is refractory to conventional therapies, or for which no conventional therapy exists, OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, PNET, rhabdoid tumor).
- Patients must have an absolute neutrophil count (ANC) > 1000/ul and a platelet count > 50,000/ul.
- Patients may have active malignancy outside the central nervous system.
- Patients who have a programmable shunt will not be excluded.
Key exclusion criteria (8 listed)
- Patients with obstructive or symptomatic communicating hydrocephalus.
- Patients with an uncontrolled life-threatening infection.
- Patients who are pregnant: Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is required during the study period.
- Patients who have received cranial or spinal irradiation less than 3 weeks prior to the start of this protocol.
- Patients who have received systemic chemotherapy (corticosteroids not included) less than 3 weeks prior to the start of this protocol.
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 |
|---|---|---|
| DNA analysis | Genetic | 131I-3F8 |
| immunologic technique | Other | 131I-3F8 |
| pharmacological study | Other | 131I-3F8 |
| iodine I 131 monoclonal antibody 3F8 | Radiation | 131I-3F8 |
| 131I-3F8Patients will receive 10mCi intrathecal 131I-3F8 per week. Patients will be pre-medicated with dexamethasone to prevent possible meningeal inflammatory reaction, Liothyronine and SSKI to prevent thyroid accumulation, and acetaminophen and diphenhydramine in anticipation of possible allergic reaction and fever. | Radiation | 131I-3F8 |
Primary outcome
Six-month Overall Survival
Time frame: 6 months
Number of Participants With Response at 6 Months
Time frame: 6 months
Complete Response (CR): Cytologic and radiographic CR will be evaluated separately, since patients with cytologic clearing and clinical response may continue to have residual abnormalities on MRI scans. Patients with a CR must also have stable or improved neurologic exam. Stable Disease (SD): Exists when a patient fails to fulfill the criteria for either complete or partial response or progressive disease. Progressive Disease (PD): An increase of at least 50% in the absolute number of malignant cells in the CSF OR, in -solid tumor patients, an increase of greater than 25% in the size of measurable lesions on MR scan OR the recurrence of malignant cells in the CSF or new lesions on MR after a patient has attained a complete remission OR evidence of clinical neurologic progression. New sites of or increasing evidence of leptomeningeal enhancement that is not "measurable" will also be considered evidence of disease progression.
1 secondary outcome
Number of Participants Evaluable for Toxicities
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kim Kramer, MD study chair
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DNA analysis, immunologic technique and pharmacological study in people with Brain and Central Nervous System Tumors and Intraocular Melanoma, run by Memorial Sloan Kettering Cancer Center 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 7 inclusion and 8 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: finished, as of the sponsor's last update on 4 Apr 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Six-month Overall Survival (time frame: 6 months). The study lists 2 primary outcomes in all. 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 4 Apr 2024.