Childhood Atypical Teratoid/Rhabdoid TumorPhase 1NCT00326664
AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors
A Phase 1 study testing Cediranib Maleate in people with Childhood Atypical Teratoid/Rhabdoid Tumor and Childhood Central Nervous System Germ Cell Tumor, run by National Cancer Institute (NCI) at 11 sites in United States.
Trial summary
This phase I trial is studying the side effects and best dose of AZD2171 in treating young patients with recurrent, progressive, or refractory primary CNS tumors. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Central Nervous System Germ Cell Tumor, Childhood Cerebral Anaplastic Astrocytoma
- What is being tested?
- Cediranib Maleate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 11 sitesUnited States
- Study dates
- Mar 2006to Jul 2015
- 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
- Histologically confirmed primary CNS tumor
- Histologically benign brain tumors (e.g., low-grade glioma) allowed
- Histological requirement waived for intrinsic brain stem or diffuse optic pathway tumors, but must have clinical and/or radiographic evidence of progression
- Recurrent, progressive, or refractory disease
- Absolute neutrophil count >= 1,000/mm^3 (unsupported)
- Platelet count >= 75,000/mm^3 (unsupported)
Show all 44Show fewer
- Creatinine =< 1.5 times upper limit of normal (ULN) OR glomerular filtration rate >= 70 mL/min
- Bilirubin =< 1.5 times ULN
- ALT =< 2.5 times ULN
- Urine dipstick or urinalysis < 1+ protein
- Albumin >= 3 g/dL
- Karnofsky performance status (PS) 60-100% (> 16 years of age) OR Lansky PS 60-100% (=< 16 years of age)
- Karnofsky/Lansky PS 70-100% for patients at increased risk for compromised LVEF
- Hemoglobin >= 8 g/dL (transfusion support allowed)
- No overt renal, hepatic, cardiac, or pulmonary disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- QTc prolongation =< 500 msec
- No other significant ECG abnormality within the past 14 days
- No clinically significant, unrelated, systemic illness, including serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction, that would preclude study participation
- No uncontrolled hypertension
- Defined as systolic and diastolic BP > 95th percentile for age (ages 1-17)
- Defined as BP > 140/90 (ages 18 and older)
- No New York Heart Association class III or IV disease and Karnofsky/Lansky PS < 70
- Class II disease controlled with treatment and increased monitoring is allowed
- Recovered from all prior therapy
- No prior AZD2171
- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas)
- More than 1 weeks since prior investigational or biologic agents
- If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration
- No concurrent drugs or biologics with proarrhythmic potential
- More than 3 months since last fraction of craniospinal radiotherapy or total-body irradiation
- More than 4 weeks since last fraction of focal irradiation to symptomatic metastatic sites
- At least 6 months since prior allogeneic bone marrow transplantation
- At least 3 months since prior autologous bone marrow or stem cell transplantation
- At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa (2 weeks for pegfilgrastim)
- No other concurrent investigational agents
- Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for ≥ 1 week before study entry
- No concurrent chemotherapy
- No concurrent routine use of G-CSF, GM-CSF, or epoetin alfa
- Able to swallow tablets
- Any neurologic deficits must be stable for >= 1 week
- If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration
Who cannot join
- No known curative therapy available
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Dana-Farber/Harvard Cancer Center
Boston, Massachusetts, 02115
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Duke University Medical Center
Durham, North Carolina, 27710
Texas Children's Hospital
Houston, Texas, 77030
Pediatric Brain Tumor Consortium
Memphis, Tennessee, 38105
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
UCSF Medical Center-Mount Zion
San Francisco, California, 94115
Seattle Children's Hospital
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase I Clinical Trial of AZD2171 in Children With Recurrent or Progressive Central Nervous System (CNS) Tumors
This phase I trial is studying the side effects and best dose of AZD2171 in treating young patients with recurrent, progressive, or refractory primary CNS tumors. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of AZD2171 in pediatric patients with recurrent, progressive, or refractory primary CNS tumors.
II. Describe the toxicity profile and dose-limiting toxicities of AZD2171 in these patients.
SECONDARY OBJECTIVES:
- Characterize inter-patient variability in the pharmacokinetics of AZD2171 in these patients.
II. Describe changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with AZD2171 at different dose levels.
III. Correlate changes in CECs, CEPs, plasma, serum, and urine levels of proteins with angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor, in patients treated with AZD2171 at different dose levels.
IV. Correlate changes in CECs, CEPs, and angiogenic modulators with changes in magnetic resonance (MR) perfusion.
- Obtain preliminary evidence of biologic activity of AZD2171 by evaluating alterations in tissue perfusion, tumor blood flow, and metabolic activity using MR perfusion and diffusion imaging, and positron-emission tomography, and correlating these findings with changes in tumor size by standard MRI.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent enzyme-inducing anticonvulsant drugs (yes vs no).
Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
For each stratum, cohorts of 2-6 patients receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients per stratum are enrolled and treated at the MTD.
After completion of study, patients are followed at 30 days.
- Conditions
- Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Central Nervous System Germ Cell Tumor, Childhood Cerebral Anaplastic Astrocytoma, Childhood Cerebral Astrocytoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma
- Being tested
- Cediranib Maleate
- Medical subject headings
- Rhabdoid Tumor, Astrocytoma, Oligodendroglioma, Spinal Cord Neoplasms, 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.
Cediranib MaleateDrug
Also called AZD2171, AZD2171 Maleate, Recentin
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cediranib maleate) | Experimental | Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cediranib Maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose, defined as the dose at which the model estimates that 25% of patients will experience dose-limiting toxicity as measured by NCI CTCAE v4.0
Estimated using the modified Continual Reassessment Method (CRM).
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2006 (estimated)
- Study startMar 2006
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Atypical Teratoid/Rhabdoid 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
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Kieran, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00326664
- Sponsor's protocol ID
- NCI-2009-00709
- Other IDs
- NCI-2009-00709, CDR0000476579, PBTC-020, PBTC-020, PBTC-020, U01CA081457
- Status last verified
- Mar 2016
- First submitted
- 16 May 2006
- Last updated
- 7 Mar 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial of AZD2171 in Children With Recurrent or Progressive Central Nervous System (CNS) Tumors
- ClinicalTrials.gov ID
- NCT00326664
- Acronym / sponsor ID
- NCI-2009-00709
- Conditions
- Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Central Nervous System Germ Cell Tumor, Childhood Cerebral Anaplastic Astrocytoma, Childhood Cerebral Astrocytoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2006
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 17 May 2006 (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 phase I trial is studying the side effects and best dose of AZD2171 in treating young patients with recurrent, progressive, or refractory primary CNS tumors. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of AZD2171 in pediatric patients with recurrent, progressive, or refractory primary CNS tumors.
II. Describe the toxicity profile and dose-limiting toxicities of AZD2171 in these patients.
SECONDARY OBJECTIVES:
- Characterize inter-patient variability in the pharmacokinetics of AZD2171 in these patients.
II. Describe changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with AZD2171 at different dose levels.
III. Correlate changes in CECs, CEPs, plasma, serum, and urine levels of proteins with angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor, in patients treated with AZD2171 at different dose levels.
IV. Correlate changes in CECs, CEPs, and angiogenic modulators with changes in magnetic resonance (MR) perfusion.
- Obtain preliminary evidence of biologic activity of AZD2171 by evaluating alterations in tissue perfusion, tumor blood flow, and metabolic activity using MR perfusion and diffusion imaging, and positron-emission tomography, and correlating these findings with changes in tumor size by standard MRI.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent enzyme-inducing anticonvulsant drugs (yes vs no).
Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
For each stratum, cohorts of 2-6 patients receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients per stratum are enrolled and treated at the MTD.
After completion of study, patients are followed at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cediranib maleate) | Experimental | Drug: Cediranib MaleatePatients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (44 listed)
- Histologically confirmed primary CNS tumor
- Recurrent, progressive, or refractory disease
- Absolute neutrophil count >= 1,000/mm^3 (unsupported)
- Platelet count >= 75,000/mm^3 (unsupported)
- Creatinine =< 1.5 times upper limit of normal (ULN) OR glomerular filtration rate >= 70 mL/min
Key exclusion criteria (1 listed)
- No known curative therapy available
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 |
|---|---|---|
| Cediranib MaleateAlso: AZD2171, AZD2171 Maleate, RecentinGiven orally | Drug | Treatment (cediranib maleate) |
Primary outcome
Maximum tolerated dose, defined as the dose at which the model estimates that 25% of patients will experience dose-limiting toxicity as measured by NCI CTCAE v4.0
Time frame: 42 days
Estimated using the modified Continual Reassessment Method (CRM).
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 7 Mar 2016.
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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.
Mark Kieran principal investigator
Pediatric Brain Tumor Consortium
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cediranib Maleate in people with Childhood Atypical Teratoid/Rhabdoid Tumor and Childhood Central Nervous System Germ Cell Tumor, 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 44 inclusion and 1 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 7 Mar 2016. 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 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?
Maximum tolerated dose, defined as the dose at which the model estimates that 25% of patients will experience dose-limiting toxicity as measured by NCI CTCAE v4.0 (time frame: 42 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 7 Mar 2016.