Central Nervous System TumorsPhase 1NCT00876993
Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors
A Phase 1 study testing Bevacizumab, Irinotecan and Temozolomide in people with Central Nervous System Tumors, run by Johns Hopkins All Children's Hospital at 1 site in United States.
Trial summary
Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Read more about this study
- Who is it for?
- Ages 18 months to 23 years
- Conditions the study is for
- Central Nervous System Tumors
- What is being tested?
- Bevacizumab, Irinotecan and Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Sep 2015
- Phase
- Phase 1
- 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 18 months to 23 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor.
- The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are high grade gliomas including brain stem gliomas.
- Age 18 months though age 23 years are eligible for this protocol.
- The patient may have received any of the agents, but not in this combination. Patients will not be eligible if they have received the combination of bevacizumab and IV irinotecan as prior therapy. They will not be eligible if they had progressive disease on any of these agents. Investigator discretion may also be used.
- Bone marrow should be recovered from prior therapy with ANC >1500 and platelets >100,000.
- Serum creatinine should be less than institutional upper limit of norm.
Show all 9Show fewer
- ALT/AST <3 times normal and bilirubin <1.5 times normal.
- Neurologic symptoms should be stable for 1 week with stable or decreasing doses of steroids.
- Patients should not be pregnant or breast feeding.
Who cannot join
- Patients with bleeding disorders or on anticoagulants.
- Uncontrolled hypertension.
- Other risks of bleeding determined on individual basis.
- Patients receiving enzyme inducing anticonvulsants.
- Patients with significant cardiac or pulmonary dysfunction that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
- For patients receiving bevacizumab, those who have had surgical procedures should not receive bevacizumab within 28 days of a major procedure, 14 days of an intermediate procedure and 7 days of a minor procedure. Lumbar punctures or placement of PICC lines are not considered minor procedures and may occur at any time prior to or during therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
About this study
Official title: A Phase I Study Of Irinotecan and Bevacizumab With Temozolomide in Children With Recurrent/Refractory Central Nervous System Tumors
Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
Read the detailed description
Bevacizumab dosing is 10 mg/kg on day 1 and day 15 of a 28 days course given IV.
Irinotecan dosing is 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the MTD of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150 mg/m2.
For dose level 0 Temozolomide, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO. Doses will be escalated according to standard phase I dose escalation criteria.
- Conditions
- Central Nervous System Tumors
- Being tested
- Bevacizumab, Irinotecan, Temozolomide
- 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.
BevacizumabDrug
Also called Irinotecan and temozolomide
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
IrinotecanDrug
Also called Bevacizumab and temozolomide
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
TemozolomideDrug
Also called Bevacizumab and irinotecan
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course. Doses will be escalated according to standard phase I dose escalation criteria. Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 0 | Experimental | Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 75 mg/m^2 PO Receives: Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide |
| Dose Level 1 | Experimental | Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 125 mg/m^2 PO Receives: Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide |
| Dose Level 2 | Experimental | Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 175 mg/m^2 PO Receives: Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide |
| Dose Level 3 | Experimental | Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 200 mg/m^2 PO Receives: Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide |
| Dose Level 4 | Experimental | Bevacizmuab 10 mg/kg IV Irinotecan 150 mg/m^2 IV Temozolomide 200 mg/m^2 PO Receives: Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Number of Adverse Events
Collect and grade the all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant.
Measured: Two 28-day cycles
Secondary outcomes (3)
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents.
Best response by MRIs per definitions in the protocol (complete response, partial response, stable disease, progressive disease). MRI's were obtained every 2 cycles and the best response was reported.
Measured: Every 2 cycles up to 24 cycles
2 Year Event Free Survival With Children Treated With This Regimen.
2 year actual event free survival.with children treated with this protocol
Measured: 2 year
To Provide Safety and Efficacy Data for to Recommend Further Larger Studies.
Number participants with grade 3 and 4 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2.
Measured: Two 28 day cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study startSep 2008
- Primary completionSep 2015
- Study completionSep 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Central Nervous System 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins All Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The V Foundation, Brain Tumor Alliance
- Responsible party
- Sponsor
- Investigators
- Stacie Stapleton, MD, Principal investigator, Johns Hopkins All Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00876993
- Sponsor's protocol ID
- ACH-CNS-001
- Status last verified
- Jun 2023
- First submitted
- 6 Apr 2009
- Last updated
- 3 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Will determine after further data analysis
Publications
Metts J, Harrington B, Salman E, Bradfield SM, Flanary J, Mosha M, Amankwah E, Stapleton S. A phase I study of irinotecan and temozolomide with bevacizumab in children with recurrent/refractory central nervous system tumors. Childs Nerv Syst. 2022 May;38(5):919-928. doi: 10.1007/s00381-022-05479-7. Epub 2022 Mar 8.
PubMed 35260913
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Of Irinotecan and Bevacizumab With Temozolomide in Children With Recurrent/Refractory Central Nervous System Tumors
- ClinicalTrials.gov ID
- NCT00876993
- Acronym / sponsor ID
- ACH-CNS-001
- Conditions
- Central Nervous System Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Johns Hopkins All Children's HospitalUniversity, hospital or other
- Collaborators
- The V Foundation, Brain Tumor Alliance
- Study start
- Sep 2008
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 7 Apr 2009 (estimated)
- Results
- Posted 8 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
Detailed description
Bevacizumab dosing is 10 mg/kg on day 1 and day 15 of a 28 days course given IV.
Irinotecan dosing is 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the MTD of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150 mg/m2.
For dose level 0 Temozolomide, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO. Doses will be escalated according to standard phase I dose escalation criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Level 0 | Experimental | Drug: Bevacizumab, Drug: Irinotecan, Drug: TemozolomideBevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 75 mg/m^2 PO |
| Dose Level 1 | Experimental | Drug: Bevacizumab, Drug: Irinotecan, Drug: TemozolomideBevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 125 mg/m^2 PO |
| Dose Level 2 | Experimental | Drug: Bevacizumab, Drug: Irinotecan, Drug: TemozolomideBevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 175 mg/m^2 PO |
| Dose Level 3 | Experimental | Drug: Bevacizumab, Drug: Irinotecan, Drug: TemozolomideBevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 200 mg/m^2 PO |
| Dose Level 4 | Experimental | Drug: Bevacizumab, Drug: Irinotecan, Drug: TemozolomideBevacizmuab 10 mg/kg IV Irinotecan 150 mg/m^2 IV Temozolomide 200 mg/m^2 PO |
Who may qualify
- Ages
- 18 months to 23 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor.
- The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are high grade gliomas including brain stem gliomas.
- Age 18 months though age 23 years are eligible for this protocol.
- The patient may have received any of the agents, but not in this combination. Patients will not be eligible if they have received the combination of bevacizumab and IV irinotecan as prior therapy. They will not be eligible if they had progressive disease on any of these agents. Investigator discretion may also be used.
- Bone marrow should be recovered from prior therapy with ANC >1500 and platelets >100,000.
Key exclusion criteria (6 listed)
- Patients with bleeding disorders or on anticoagulants.
- Uncontrolled hypertension.
- Other risks of bleeding determined on individual basis.
- Patients receiving enzyme inducing anticonvulsants.
- Patients with significant cardiac or pulmonary dysfunction that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
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 |
|---|---|---|
| BevacizumabAlso: Irinotecan and temozolomideBevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle | Drug | Dose Level 0, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4 |
| IrinotecanAlso: Bevacizumab and temozolomideIrinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2. | Drug | Dose Level 0, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4 |
| TemozolomideAlso: Bevacizumab and irinotecanFor the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course. Doses will be escalated according to standard phase I dose escalation criteria. Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2) | Drug | Dose Level 0, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4 |
Primary outcome
Measurement of Number of Adverse Events
Time frame: Two 28-day cycles
Collect and grade the all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant.
3 secondary outcomes
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents.
Time frame: Every 2 cycles up to 24 cycles
2 Year Event Free Survival With Children Treated With This Regimen.
Time frame: 2 year
To Provide Safety and Efficacy Data for to Recommend Further Larger Studies.
Time frame: Two 28 day cycles
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35260913Metts J, Harrington B, Salman E, Bradfield SM, Flanary J, Mosha M, Amankwah E, Stapleton S. A phase I study of irinotecan and temozolomide with bevacizumab in children with recurrent/refractory central nervous system tumors. Childs Nerv Syst. 2022 May;38(5):919-928. doi: 10.1007/s00381-022-05479-7. Epub 2022 Mar 8.
- Individual participant dataSharing planned: Undecided. Will determine after further data analysis
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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.
Stacie Stapleton, MD principal investigator
Johns Hopkins All Children's Hospital
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 Bevacizumab, Irinotecan and Temozolomide in people with Central Nervous System Tumors, run by Johns Hopkins All Children's Hospital 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 9 inclusion and 6 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 3 Jul 2023. 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?
Yes. Results are posted in the registry (first posted 8 Aug 2019). 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?
Measurement of Number of Adverse Events (time frame: Two 28-day cycles). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00876993, which also lists 1 linked publication.
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 3 Jul 2023; AzTrials last refreshed its copy on 7 Nov 2026.