Childhood Central Nervous System Germ Cell TumorPhase 1NCT00052780
Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors
A Phase 1 study testing O6-benzylguanine, temozolomide and filgrastim in people with Childhood Central Nervous System Germ Cell Tumor and Childhood Choroid Plexus Tumor, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma
- What is being tested?
- O6-benzylguanine, temozolomide and filgrastim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2002to Nov 2007
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Recurrent or refractory pediatric brain tumors; a histopathologic diagnosis from either the initial presentation or at the time of recurrence is required for all but brain stem gliomas
- Karnofsky or Lansky ≥ 60%
- Life expectancy > 8 weeks
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to study entry
- Chemotherapy: No more than 2 previous chemotherapy/biologic therapy regimens; evidence of recovery from prior chemotherapy/biologic therapy; no myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) of study entry; patients who have received temozolomide are eligible if they have not received the drug in the past 3 months and did not experience any non-hematopoietic Grade 3/4 toxicity with prior temozolomide therapy
- XRT: ≥ 3 months prior to study entry for craniospinal irradiation (≥ 18 Gy); ≥ 4 weeks for local radiation to primary tumor; and ≥ 2 weeks prior to study entry for focal irradiation to symptomatic metastatic sites
Show all 22Show fewer
- Bone Marrow Transplant: ≥ 6 months prior to study entry
- Anti-convulsants: Patients will be eligible for this study even if they are receiving anti-convulsants
- Growth factors: Off all colony forming growth factor(s) > 2 weeks prior to study entry (G-CSF, GM-CSF, Erythropoietin)
- Dexamethasone: Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
- ANC > 1,000/μl
- Platelets > 100,000/μl
- Hemoglobin > 8g/dl
- Patients may have bone marrow involvement by disease; platelet and Hgb counts must be transfusion independent
- Creatinine ≤ 1.5 times institutional normal for age
- Or GFR > 70 ml/min/1.73m^2
- Bilirubin ≤ upper limit of normal for age
- SGPT (ALT) < and SGOT (AST) < 2.5X institutional normal
- No overt renal, hepatic, cardiac or pulmonary disease
- Female patients of childbearing potential must have negative serum or urine pregnancy test; patient must not be pregnant or breast-feeding; while no known teratogenic effects are known for O6-BG so far, there is little data to address this specifically; as such, the prudent approach is to exclude pregnant and breastfeeding patients until further data is available
- Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
- Signed informed consent according to institutional guidelines must be obtained and patients must begin therapy within seven (7) days of registration
Who cannot join
- Patients must not be receiving any other anticancer or experimental drug therapy
- Patients with a history of hypersensitivity to dacarbazine, temozolomide or polyethylene glycol are excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Pediatric Brain Tumor Consortium
Memphis, Tennessee, 38105
About this study
Official title: Phase I Trial of Temozolomide and O6-Benzylguanine in Pediatric Patients With Recurrent Brain Tumors
Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of temozolomide (Temodar) when administered with O6-benzylguanine (O6-BG) with and without G-CSF support to pediatric patients with refractory brain tumors stratified by previous radiotherapy.
SECONDARY OBJECTIVES:
- To characterize the pharmacokinetics of temozolomide and O6-BG when used in combination.
II. To characterize toxicities associated with the combination of O6-BG and temozolomide with and without G-CSF support.
III. To document antitumor response in patients when treated with O6-BG and temozolomide.
IV. To determine the levels of MGMT enzyme and mismatch repair (MMR) proteins in tumor tissue, investigating a possible correlation with patient outcome.
OUTLINE: This is a dose-escalation study of temozolomide with and without filgrastim (G-CSF). Patients are stratified according to prior radiotherapy (RT)/myeloablative therapy (no RT or focal RT vs craniospinal RT or myeloablative therapy).
Patients receive O6-benzylguanine IV continuously on days 1 and 2 and oral temozolomide on day 1. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 2-6 patients in each stratum receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience DLT. Once the MTD is determined, additional patients are treated at that dose level for a total of 12 patients treated at the MTD.
For courses 1-12, patients experiencing neutropenia may also receive G-CSF subcutaneously or IV daily beginning on day 3 and continuing until blood counts recover.
If neutropenia is the dose-limiting toxicity (DLT) for the first 2 strata, patients are further stratified according to concurrent G-CSF support (yes vs no).Cohorts of 3-6 patients in each stratum receive escalating doses of temozolomide with G-CSF until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience DLT. Once the MTD is determined, 6 additional patients are treated at that dose.
Patients are followed for resolution of all adverse events occurring while on treatment and/or within 30 days of the last administration of study drug. Patients will be followed for the shortest of 1) three months after the last protocol based treatment, or 2) the date other therapy is initiated.
- Conditions
- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma, Childhood Ependymoblastoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma
- Being tested
- O6-benzylguanine, temozolomide, filgrastim, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Choroid Plexus Neoplasms, Astrocytoma, Oligodendroglioma, Familial ependymoma, Medulloblastoma, Optic Nerve Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
O6-benzylguanineDrug
Also called BG
Given IV
temozolomideDrug
Also called SCH 52365, Temodal, Temodar, TMZ
Given PO
filgrastimBiological
Also called G-CSF, Neupogen
Given SC or IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (temozolomide, O6-benzylguanine) | Experimental | See Detailed Description Receives: Drug: O6-benzylguanine; Drug: temozolomide; Biological: filgrastim; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of temozolomide
Measured: 28 days
Secondary outcomes (6)
Pharmacokinetic parameters
Summarized using descriptive statistics (mean, standard deviation) if normally distributed. For log-normally distributed data, the geometric mean will be used. If the data are not normally distributed, nonparametric statistics (median, minimum, maximum, interquartile ranges) will be used. Logistic regression models will be used to explore possible relationships between the systemic exposure to temozolomide, O6-benzylguanine, and their respective metabolites and toxicities and antitumor activity.
Measured: Baseline and courses 1 and 3
Acute toxicities
These toxicities will be tabulated according to dose level.
Measured: 4 weeks (course 1)
Chronic toxicities
Tabulated according to dose level and course of therapy.
Measured: Up to 30 days post-treatment
Histological response
Exact confidence interval estimates of traditional response by histologic tumor type will be developed.
Measured: Up to 5 years
Duration of disease control
Kaplan-Meier estimates will also be provided.
Measured: Up to 5 years
Survival
Kaplan-Meier estimates will also be provided.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startOct 2002
- Primary completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Central Nervous System Germ Cell TumorStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Amar Gajjar, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00052780
- Sponsor's protocol ID
- NCI-2012-03174
- Other IDs
- NCI-2012-03174, CDR653709, PBTC-005, PBTC-005, U01CA081457
- Status last verified
- Sep 2013
- First submitted
- 24 Jan 2003
- Last updated
- 30 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Temozolomide and O6-Benzylguanine in Pediatric Patients With Recurrent Brain Tumors
- ClinicalTrials.gov ID
- NCT00052780
- Acronym / sponsor ID
- NCI-2012-03174
- Conditions
- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma, Childhood Ependymoblastoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2002
- Primary completion
- Nov 2007 (actual)
- First posted
- 27 Jan 2003 (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.
Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of temozolomide (Temodar) when administered with O6-benzylguanine (O6-BG) with and without G-CSF support to pediatric patients with refractory brain tumors stratified by previous radiotherapy.
SECONDARY OBJECTIVES:
- To characterize the pharmacokinetics of temozolomide and O6-BG when used in combination.
II. To characterize toxicities associated with the combination of O6-BG and temozolomide with and without G-CSF support.
III. To document antitumor response in patients when treated with O6-BG and temozolomide.
IV. To determine the levels of MGMT enzyme and mismatch repair (MMR) proteins in tumor tissue, investigating a possible correlation with patient outcome.
OUTLINE: This is a dose-escalation study of temozolomide with and without filgrastim (G-CSF). Patients are stratified according to prior radiotherapy (RT)/myeloablative therapy (no RT or focal RT vs craniospinal RT or myeloablative therapy).
Patients receive O6-benzylguanine IV continuously on days 1 and 2 and oral temozolomide on day 1. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 2-6 patients in each stratum receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience DLT. Once the MTD is determined, additional patients are treated at that dose level for a total of 12 patients treated at the MTD.
For courses 1-12, patients experiencing neutropenia may also receive G-CSF subcutaneously or IV daily beginning on day 3 and continuing until blood counts recover.
If neutropenia is the dose-limiting toxicity (DLT) for the first 2 strata, patients are further stratified according to concurrent G-CSF support (yes vs no).Cohorts of 3-6 patients in each stratum receive escalating doses of temozolomide with G-CSF until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience DLT. Once the MTD is determined, 6 additional patients are treated at that dose.
Patients are followed for resolution of all adverse events occurring while on treatment and/or within 30 days of the last administration of study drug. Patients will be followed for the shortest of 1) three months after the last protocol based treatment, or 2) the date other therapy is initiated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (temozolomide, O6-benzylguanine) | Experimental | Drug: O6-benzylguanine, Drug: temozolomide, Biological: filgrastim, Other: pharmacological study, Other: laboratory biomarker analysisSee Detailed Description |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- Recurrent or refractory pediatric brain tumors; a histopathologic diagnosis from either the initial presentation or at the time of recurrence is required for all but brain stem gliomas
- Karnofsky or Lansky ≥ 60%
- Life expectancy > 8 weeks
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to study entry
- Chemotherapy: No more than 2 previous chemotherapy/biologic therapy regimens; evidence of recovery from prior chemotherapy/biologic therapy; no myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) of study entry; patients who have received temozolomide are eligible if they have not received the drug in the past 3 months and did not experience any non-hematopoietic Grade 3/4 toxicity with prior temozolomide therapy
Key exclusion criteria (2 listed)
- Patients must not be receiving any other anticancer or experimental drug therapy
- Patients with a history of hypersensitivity to dacarbazine, temozolomide or polyethylene glycol are excluded
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 |
|---|---|---|
| O6-benzylguanineAlso: BGGiven IV | Drug | Treatment (temozolomide, O6-benzylguanine) |
| temozolomideAlso: SCH 52365, Temodal, Temodar, TMZGiven PO | Drug | Treatment (temozolomide, O6-benzylguanine) |
| filgrastimAlso: G-CSF, NeupogenGiven SC or IV | Biological | Treatment (temozolomide, O6-benzylguanine) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (temozolomide, O6-benzylguanine) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (temozolomide, O6-benzylguanine) |
Primary outcome
MTD of temozolomide
Time frame: 28 days
6 secondary outcomes
Pharmacokinetic parameters
Time frame: Baseline and courses 1 and 3
Acute toxicities
Time frame: 4 weeks (course 1)
Chronic toxicities
Time frame: Up to 30 days post-treatment
Histological response
Time frame: Up to 5 years
Duration of disease control
Time frame: Up to 5 years
Survival
Time frame: Up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2013.
Related trials for Childhood Central Nervous System Germ Cell Tumor
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
RecruitingPhase 1
Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer
Ependymoma, Medulloblastoma
Active, not recruitingPhase 2
Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
Glioblastoma, Medulloblastoma
RecruitingPhase 2
Illuminate: A Clinical Study Evaluating CAR T Immune Cell Therapy (BCB-276) for Patients With Diffuse Intrinsic Pontine Glioma (DIPG).
Diffuse Intrinsic Pontine Glioma, DIPG
RecruitingPhase 1
Phase I Trial to Determine the Dose and Evaluate the PK and Safety of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors
Somatostatin Receptor Positive, NETs
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.
Amar Gajjar principal investigator
Pediatric Brain Tumor Consortium
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 O6-benzylguanine, temozolomide and filgrastim in people with Childhood Central Nervous System Germ Cell Tumor and Childhood Choroid Plexus Tumor, run by National Cancer Institute (NCI) 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 22 inclusion and 2 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 30 Sep 2013. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
MTD of temozolomide (time frame: 28 days). 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 30 Sep 2013.