Brain and Central Nervous System TumorsPhase 2NCT00275002
O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors
A Phase 2 study testing O6-benzylguanine and temozolomide in people with Brain and Central Nervous System Tumors, run by National Cancer Institute (NCI) at 11 sites in United States.
Trial summary
This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- O6-benzylguanine and temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 11 sitesUnited States
- Study dates
- Feb 2006to Dec 2010
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Tumor: Participants must have a high-grade glioma (including e.g. histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic confirmation waived) with documentation of disease recurrence or progression after treatment with standard therapy. Participants must have bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions
- Age: 21 years of age or less
- Performance status: Karnofsky 60-100% (for patients > 16 years of age) or Lansky 60-100% (for patients ≤ 16 years of age)
- Life expectancy: Not specified
- Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL (may be supported), and absolute lymphocyte count ≥ 500/mm^3
- Hepatic: Must have SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN, and no overt hepatic disease
Show all 16Show fewer
- Renal: Participants must have creatinine clearance ≥ 60 mL/min or creatinine based on age as follows: no greater than 0.8 mg/dL (for patients ≤ 5 years of age), no greater than 1.0 mg/dL (for patients 6 to 10 years of age), no greater than 1.2 mg/dL (for patients 11 to 15 years of age), or no greater than 1.5 mg/dL (for patients > 15 years of age). There must be no overt renal disease
- Cardiovascular: Must have no overt cardiac disease
- Pulmonary: Must have no overt pulmonary disease
- Other: Female participants of childbearing potential must have a negative pregnancy test prior to study registration, and must avoid breast-feeding. Female and male participants of childbearing or child-fathering potential must use effective contraception
- Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow transplantation and at least 3 months since prior autologous bone marrow or stem cell transplantation
- Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)
- Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer chemotherapy ≥ 3 weeks prior to study registration and ≥ 6 weeks for nitrosoureas. Must have received last dose of nonmyelosuppressive investigational agents or anticancer drugs ≥ 7 days prior to study registration. Participants who have received prior temozolomide are eligible
- Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed
- Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and local irradiation to the primary tumor ≥ 12 weeks prior to study registration
- Prior Therapy-Other: Must have recovered from all prior therapy
Who cannot join
- Must not have history of severe toxicity (≥ grade 3) associated with temozolomide
- Must not be receiving other concurrent anticancer or investigational therapy
- Must not have history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG)
- Must not have uncontrolled significant systemic illness including infection, or overt renal, hepatic, cardiac, or pulmonary disease
- Must not be HIV positive
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60614
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, 77030-2399
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, 77030
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
About this study
Official title: A Phase II Trial of O6-Benzylguanine and Temozolomide in Pediatric Patients With Recurrent or Progressive High-Grade Gliomas and Recurrent or Progressive Brainstem Tumors
This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the sustained objective response rate to the combination of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brain stem tumors.
SECONDARY OBJECTIVES:
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (high-grade gliomas vs brain stem tumors).
Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed to the earliest of 30 days following discontinuation of therapy or the initiation of additional anti-cancer therapy or death.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- O6-benzylguanine, temozolomide
- Keywords
- recurrent childhood brain stem glioma, recurrent childhood brain tumor
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
O6-benzylguanineDrug
Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. O6-Benzylguanine, 120 mg/m^2, will be administered as a one-hour intravenous (IV) infusion, daily for 5 days. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses of therapy.
temozolomideDrug
Also called Temodar
Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Temozolomide, 75 mg/m^2 (rounded to the nearest 5 mg, the size of the smallest capsule) will be given orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses.
| Study group | Role | What they receive |
|---|---|---|
| O6-BG and TMZ | Experimental | O6-benzylguanine (O6-BG) and temozolomide (TMZ) Receives: Drug: O6-benzylguanine; Drug: temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With an Objective Response (Complete Response or Partial Response)
The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.
Measured: Week 8, 16, 24, 32, and 40 after starting therapy
Secondary outcomes (1)
Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide
Clinical and laboratory studies to assess adverse events are obtained at least every four weeks (prior to each course) with some laboratory studies obtained every 2 weeks. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Attribution of each adverse event to the treatment regimen is determined by the participant's attending physician at the enrolling institution and verified by the study chair.
Measured: From day 1 of therapy up to 49 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2006 (estimated)
- Study startFeb 2006
- Primary completion1 Dec 2010
- Study completionDec 2010
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 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Katherine Warren, MD, Study chair, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00275002
- Sponsor's protocol ID
- NCI-2012-03050
- Other IDs
- PBTC-015, NCI-06-C-0089, NCI-P6692, CDR0000455561
- Status last verified
- Jan 2022
- First submitted
- 10 Jan 2006
- Last updated
- 11 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of O6-Benzylguanine and Temozolomide in Pediatric Patients With Recurrent or Progressive High-Grade Gliomas and Recurrent or Progressive Brainstem Tumors
- ClinicalTrials.gov ID
- NCT00275002
- Acronym / sponsor ID
- NCI-2012-03050
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- recurrent childhood brain stem glioma, recurrent childhood brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2006
- Primary completion
- 1 Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 11 Jan 2006 (estimated)
- Results
- Posted 9 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the sustained objective response rate to the combination of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brain stem tumors.
SECONDARY OBJECTIVES:
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (high-grade gliomas vs brain stem tumors).
Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed to the earliest of 30 days following discontinuation of therapy or the initiation of additional anti-cancer therapy or death.
PROJECTED ACCRUAL: A total of 50 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 |
|---|---|---|
| O6-BG and TMZ | Experimental | Drug: O6-benzylguanine, Drug: temozolomideO6-benzylguanine (O6-BG) and temozolomide (TMZ) |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Tumor: Participants must have a high-grade glioma (including e.g. histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic confirmation waived) with documentation of disease recurrence or progression after treatment with standard therapy. Participants must have bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in ≥ 2 dimensions
- Age: 21 years of age or less
- Performance status: Karnofsky 60-100% (for patients > 16 years of age) or Lansky 60-100% (for patients ≤ 16 years of age)
- Life expectancy: Not specified
- Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL (may be supported), and absolute lymphocyte count ≥ 500/mm^3
Key exclusion criteria (5 listed)
- Must not have history of severe toxicity (≥ grade 3) associated with temozolomide
- Must not be receiving other concurrent anticancer or investigational therapy
- Must not have history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG)
- Must not have uncontrolled significant systemic illness including infection, or overt renal, hepatic, cardiac, or pulmonary disease
- Must not be HIV positive
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-benzylguanineDosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. O6-Benzylguanine, 120 mg/m^2, will be administered as a one-hour intravenous (IV) infusion, daily for 5 days. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses of therapy. | Drug | O6-BG and TMZ |
| temozolomideAlso: TemodarDosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Temozolomide, 75 mg/m^2 (rounded to the nearest 5 mg, the size of the smallest capsule) will be given orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course. Courses will be repeated every 4 weeks for up to 12 courses. | Drug | O6-BG and TMZ |
Primary outcome
Percentage of Participants With an Objective Response (Complete Response or Partial Response)
Time frame: Week 8, 16, 24, 32, and 40 after starting therapy
The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.
1 secondary outcome
Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide
Time frame: From day 1 of therapy up to 49 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- 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.
Katherine Warren, MD study chair
National Cancer Institute (NCI)
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing O6-benzylguanine and temozolomide in people with Brain and Central Nervous System Tumors, run by National Cancer Institute (NCI) at 11 sites 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 16 inclusion and 5 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 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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 9 Aug 2011). 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?
Percentage of Participants With an Objective Response (Complete Response or Partial Response) (time frame: Week 8, 16, 24, 32, and 40 after starting therapy). 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 11 Feb 2022.