Refractory Brain TumorsPhase 1NCT00836628
Study of Busulfan for Refractory Central Nervous System (CNS) Tumors
A Phase 1 study testing Busulfan in people with Refractory Brain Tumors, run by Ann & Robert H Lurie Children's Hospital of Chicago.
Trial summary
This protocol is aimed at establishing a maximum tolerated dose (MTD) for submyeloablative doses of Busulfex ® with the hope that a tolerable, submyeloablative dose can be established to test efficacy as alternative therapy for refractory pediatric brain tumors. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Refractory Brain Tumors
- What is being tested?
- Busulfan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2008to Oct 2010
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Age >2 year and ≤ 21 years Histologic Diagnosis Any histological proven (confirmed by institutional pathology report; pathology slides from outside referring outside institutions are not required.) recurrent or progressive CNS tumor. (optic pathway and brainstem gliomas allowed without histologic verification, but must have diagnostic imaging).
- Life Expectancy Patients must have a life expectancy of ≥ 2 months. Prior Therapy There is no limit to the number of prior therapies a patient has received
- Must be ≥ 3 weeks from myelosuppressive chemotherapy (6 weeks from nitrosoureas) and have demonstrated recovery (ANC ≥ 1000/uL) from their last course of chemotherapy
- ≥ 6 months following allogeneic stem cell transplantation
- ≥ 3 months following autologous stem cell transplantation
- ≥ 3 months from craniospinal radiation
Show all 26Show fewer
- ≥ 4 weeks from focal radiation
- ≥ 7 days from any past biologic/immunotherapy
- ≥ 1 week from any hematopoietic growth factors Concomitant Medication
- Patients taking Itraconazole or Phenytoin will be excluded. Patients must be off of these medications for at least 3 days prior to entering this trial. If the patient is taking phenytoin for seizures at the time of study enrollment, it must be stopped at least 3 days prior to starting therapy and Clonazepam will be substituted during the Busulfex ® infusions and for 24 hours following the infusion.
- Patients on growth stimulating factors, such as GCSF, will be allowed to continue these medications only as indicated in the study.
- Patients may be taking steroids while participating in this trial, but should be on a stable dose for >1 week prior to enrollment.
- Medications interacting with the CYP3A4 substrate should also be avoided while the patient is on study.
- Patients should also be on Pneumocystis prophylaxis while participating in this study. Pentamidine will be required, with a recommended dose of 4 mg/kg given intravenously every month. Pentamidine should continue throughout the duration of the trial.
- Organ Function Requirements Adequate Bone Marrow Function Defined As
- Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/ul (off growth factors x 48 hrs)
- Platelet count greater than or equal to 100,000/uL (transfusion independent)
- Hemoglobin greater than or equal to 8.0 gm/dL (may receive RBC transfusions) Adequate Renal Function Defined As
- Serum creatinine less than or equal to 1.5 x upper limit of normal, or
- Estimated creatinine clearance GFR greater than or equal to 70 ml/min/1.73 m² by the Schwartz formula Adequate Liver Function Defined As
- Total bilirubin within normal range
- SGPT (ALT) within normal range Adequate Pulmonary Function Defined As
- Oxygen saturation >92% on room air Central Nervous System Function Defined As
- Patients with seizure disorder may be enrolled; Patients MUST be on an anti-seizure medication upon enrollment, but this medication CANNOT be phenytoin or carbamezepine.
- Patients must not be in status, coma or assisted ventilation prior to study enrollment.
- Stable neurologic exam of at least 1 week duration Performance Level Karnofsky/ Lansky 50 or greater
Who cannot join
- Pregnancy/Contraception: patients who are pregnant or breast-feeding will not be eligible.
- Patients of childbearing potential must practice an effective method of birth control while participating on the study.
- Females > 13 years of age or those who have achieved menarche must have a negative pregnancy test prior to study entry.
About this study
Official title: A Phase I Study Using Submyeloablative DOsing of Intravenous Busulfan (Busulfex) for Refractory Brain Tumors
This protocol is aimed at establishing a maximum tolerated dose (MTD) for submyeloablative doses of Busulfex ® with the hope that a tolerable, submyeloablative dose can be established to test efficacy as alternative therapy for refractory pediatric brain tumors.
Read the detailed description
Pediatric brain tumors remain among the most common malignancies in childhood, second only to leukemia, representing 20% of all childhood cancers in the United States (1). Although significant strides have been made in therapies for other pediatric malignancies, mortality for patients with brain tumors remains high. The mainstay of therapy for CNS tumors has been a combination of surgery, chemotherapy, and radiation. High dose chemotherapy with stem cell transplant has been proposed as an alternative to radiation, in very young children and for relapsed patients. Stem cell transplantation however is not without significant side effects as well as transplant related mortality.
Busulfan is an alkylating agent and is able to exert its cytotoxic effects through hydrolysis and subsequent production of carbonium ions, directly alkylating DNA, interfering with its replication, and ultimately leading to cell death (2). Busulfan readily crosses the blood barrier, allowing for CNS levels nearly equal to those of plasma levels (5,6).
Primary Objectives:
To determine the maximum tolerated dose (MTD) of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors.
Secondary Objectives:
To obtain preliminary data regarding progression free survival (PFS) and event free survival (EFS) when Busulfex ® is used at submyeloablative doses in children with recurrent, progressive, or refractory primary brain tumors.
To describe the plasma pharmacokinetics of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors, using a continuous infusion.
- Conditions
- Refractory Brain Tumors
- Being tested
- Busulfan
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex ®
| Study group | Role | What they receive |
|---|---|---|
| experimental | Experimental | Not described Receives: Drug: Busulfan |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2009 (estimated)
- Study startJul 2008
- Primary completionOct 2010
- Study completionOct 2010
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Brain TumorsStudies of the same condition, open and under way.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stewart Goldman, Ann & Robert H Lurie Children's Hospital of Chicago
- Investigators
- Stewart Goldman, MD, Principal investigator, Ann & Robert H Lurie Children's Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00836628
- Sponsor's protocol ID
- CNS 1100
- Status last verified
- Aug 2020
- First submitted
- 3 Feb 2009
- Last updated
- 5 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Using Submyeloablative DOsing of Intravenous Busulfan (Busulfex) for Refractory Brain Tumors
- ClinicalTrials.gov ID
- NCT00836628
- Acronym / sponsor ID
- CNS 1100
- Conditions
- Refractory Brain Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: slow accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of ChicagoUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 4 Feb 2009 (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.
This protocol is aimed at establishing a maximum tolerated dose (MTD) for submyeloablative doses of Busulfex ® with the hope that a tolerable, submyeloablative dose can be established to test efficacy as alternative therapy for refractory pediatric brain tumors.
Detailed description
Pediatric brain tumors remain among the most common malignancies in childhood, second only to leukemia, representing 20% of all childhood cancers in the United States (1). Although significant strides have been made in therapies for other pediatric malignancies, mortality for patients with brain tumors remains high. The mainstay of therapy for CNS tumors has been a combination of surgery, chemotherapy, and radiation. High dose chemotherapy with stem cell transplant has been proposed as an alternative to radiation, in very young children and for relapsed patients. Stem cell transplantation however is not without significant side effects as well as transplant related mortality.
Busulfan is an alkylating agent and is able to exert its cytotoxic effects through hydrolysis and subsequent production of carbonium ions, directly alkylating DNA, interfering with its replication, and ultimately leading to cell death (2). Busulfan readily crosses the blood barrier, allowing for CNS levels nearly equal to those of plasma levels (5,6).
Primary Objectives:
To determine the maximum tolerated dose (MTD) of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors.
Secondary Objectives:
To obtain preliminary data regarding progression free survival (PFS) and event free survival (EFS) when Busulfex ® is used at submyeloablative doses in children with recurrent, progressive, or refractory primary brain tumors.
To describe the plasma pharmacokinetics of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors, using a continuous infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| experimental | Experimental | Drug: Busulfan |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (26 listed)
- Age: Age >2 year and ≤ 21 years Histologic Diagnosis Any histological proven (confirmed by institutional pathology report; pathology slides from outside referring outside institutions are not required.) recurrent or progressive CNS tumor. (optic pathway and brainstem gliomas allowed without histologic verification, but must have diagnostic imaging).
- Life Expectancy Patients must have a life expectancy of ≥ 2 months. Prior Therapy There is no limit to the number of prior therapies a patient has received
- Must be ≥ 3 weeks from myelosuppressive chemotherapy (6 weeks from nitrosoureas) and have demonstrated recovery (ANC ≥ 1000/uL) from their last course of chemotherapy
- ≥ 6 months following allogeneic stem cell transplantation
- ≥ 3 months following autologous stem cell transplantation
Key exclusion criteria (3 listed)
- Pregnancy/Contraception: patients who are pregnant or breast-feeding will not be eligible.
- Patients of childbearing potential must practice an effective method of birth control while participating on the study.
- Females > 13 years of age or those who have achieved menarche must have a negative pregnancy test prior to study entry.
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 |
|---|---|---|
| BusulfanAlso: Busulfex ® | Drug | experimental |
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Individual participant dataSharing planned: Undecided
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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.
Stewart Goldman, MD principal investigator
Ann & Robert H Lurie Children's Hospital of Chicago
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Busulfan in people with Refractory Brain Tumors, run by Ann & Robert H Lurie Children's Hospital of Chicago.
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 26 inclusion and 3 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: withdrawn, as of the sponsor's last update on 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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.
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 5 Aug 2020.