Recurrent Childhood Brain TumorSEEDNCT02015728
Selecting Patient-Specific Biologically Targeted Therapy for Pediatric Patients With Refractory Or Recurrent Brain Tumors
A study testing Tumor biology testing, Temozolomide and Etoposide in people with Recurrent Childhood Brain Tumor, run by Seattle Children's Hospital at 1 site in United States.
Trial summary
This research study is a Feasibility clinical trial. In this trial, researchers are trying to figure out whether a medication can be chosen based on rapid testing done on tumor tissue. Read more about this study
- Who is it for?
- Ages 1 month to 30 years
- Conditions the study is for
- Recurrent Childhood Brain Tumor
- What is being tested?
- Tumor biology testing, Temozolomide and Etoposide
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Dec 2017
- Phase
- Interventional
- 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 1 month to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must have histological confirmation of a brain tumor at diagnosis or relapse for all tumors.
- There must be documented progression or recurrence of disease by MRI imaging or CSF studies since completion of last tumor-directed medical therapy. Patients may have had surgical resection or radiation of tumor, and need not have measurable or evaluable disease at study entry.
- Patient's current disease state must be one for which there is no known curative therapy.
- Age greater than 1 month and less than 30 years at the time of enrollment.
- BSA greater than 0.3 m2 at the time of enrollment.
- Karnofsky >/= 50% for patients > 16 years of age, and Lansky >/= 50% for patients </= 16 years of age.
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- Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 7 days.
- Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Adequate bone marrow function including:
- ANC > 750
- Platelet count > 100,000/uL without platelet transfusion within the past 7 days
- Adequate renal function defined as creatinine within normal range for age or calculated GFR > 100 ml/min/1.73 m2.
- Adequate liver function defined as Bilirubin < 1.5 x upper limit of normal and ALT < 2.5 x upper limit of normal.
- Adequate CNS function:
- Patients with known seizure disorder must have seizures adequately controlled with non-enzyme inducing antiepileptic medications
- No increase in steroid dose within the past 7 days.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy:
- Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea).
- Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor, 14 days for longacting (e.g. PEG-filgrastim)
- Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is longer) since the completion of therapy with a biologic agent.
- Radiation therapy: ≥ 12 weeks must have elapsed from craniospinal radiation; ≥ 2 weeks must have elapsed from focal radiation.
- Surgery: > 3 weeks from major surgery. If recent craniotomy, adequate wound healing must be determined by neurosurgical team prior to starting study therapy.
- Autologous Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 4 weeks must have elapsed.
- All patients and/or a legal guardian must sign institutionally approved written informed consent document.
Who cannot join
- Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded. Abstinence is considered an effective form of birth control.
- Patients with uncontrolled infection are excluded.
- Patients with known bleeding disorders or more than punctate intratumoral hemorrhage are excluded.
- Patients receiving other anti-neoplastic agents are excluded.
- Patients on enzyme-inducing anticonvulsive agents are excluded.
- Patients requiring strong CYP3A4 inducers or inhibitors are excluded.
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- Patients requiring anticoagulation or with uncontrolled bleeding are excluded.
- Patients on steroids for symptom management must be on a stable dose over the 7 days prior to study enrollment.
- Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD or requiring immunosuppression are excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy With Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric Patients With Refractory Or Recurrent Brain Tumors
This research study is a Feasibility clinical trial. In this trial, researchers are trying to figure out whether a medication can be chosen based on rapid testing done on tumor tissue. Information from a feasibility or pilot trial will hopefully help researchers plan larger trials in the future to determine the effect of this therapy.
Read the detailed description
This research study will assign a specific drug treatment based on lab tests performed on the participant's tumor from tumor tissue taken from a biopsy done when he/she was first diagnosed or if taken when he/she relapsed or progressed. All participants will get Temozolomide and Etoposide to start. Then depending on review of the participant's tumor tissue he/she will also receive one of the following: Sorafenib, Everolimus, Erlotinib, or Dasatinib.
The purpose of this research study is to learn about the feasibility of obtaining and using information from studies done on tumor tissue in order to help make treatment decisions for patients with relapsed or refractory pediatric brain tumors. The investigators also want to find out the effects this therapy has on the participant and the participant's brain tumor.
- Conditions
- Recurrent Childhood Brain Tumor
- Being tested
- Tumor biology testing, Temozolomide, Etoposide, Sorafenib, Everolimus
- Keywords
- Refractory, Recurrent, Brain, Tumor, Pediatric, Biologically Targeted Therapy, Sorafenib, Everolimus, Erlotinib, Dasatinib, Temozolomide, Etoposide
- Medical subject headings
- Recurrence, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor biology testingDevice
Also called IHC Testing, Immunohistochemical Screening, Immunohistochemical Test, Tumor Markers
Tumor biology studies will be performed in a CLIA-approved clinical pathology laboratory using standard procedures. Immunohistochemical (IHC) testing will be performed on formalin fixed tumor obtained at the time of diagnosis and/or relapse. Results will be interpreted by a qualified pediatric pathologist and will be scored on a scale of 0 to 4+ commenting on both percentage of positive cells and intensity of staining. Results will further be reported as a binary result (positive/negative). If more than one tumor specimen is available from different surgical procedures (e.g. initial diagnosis and relapse), the results from the relapse specimen will be prioritized. Results will determine kinase inhibitor treatment arm assignment which will be administered in addition to the "best available" combination of low-dose oral cytotoxic agents, including temozolomide and etoposide.
TemozolomideDrug
Also called Temodar, Temodal, Temcad
Temozolomide combined with Etoposide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors.
EtoposideDrug
Also called Etopophos, Vepesid
Etoposide combined with Temozolomide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors.
SorafenibDrug
Also called Nexavar
Sorafenib is a broad-spectrum kinase inhibitor.
EverolimusDrug
Also called Zortress, Certican
Everolimus is an mTOR pathway inhibitor.
ErlotinibDrug
Also called Tarceva
Erlotinib is a tyrosine kinase inhibitor of the ERBB family of proteins.
DasatinibDrug
Also called Sprycel
Dasatinib is a broad spectrum SRC inhibitor.
| Study group | Role | What they receive |
|---|---|---|
| Regimen B | Experimental | Depending on tumor biology testing, subjects assigned to Regimen B will receive:
Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Everolimus 3 mg/m2/dose daily PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. Receives: Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Everolimus |
| Regimen C | Experimental | Depending on tumor biology testing, subjects assigned to Regimen C will receive:
Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Erlotinib 85 mg/m2/dose daily PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. Receives: Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Erlotinib |
| Regimen D | Experimental | Depending on tumor biology testing, subjects assigned to Regimen D will receive:
Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Dasatinib 60 mg/m2/dose BID PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. Receives: Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Dasatinib |
| Regimen A | Experimental | Depending on tumor biology testing, subjects assigned to Regimen A will receive:
Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Sorafenib 150 mg/m2/dose BID PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. Receives: Device: Tumor biology testing; Drug: Temozolomide; Drug: Etoposide; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility
It will be considered feasible to obtain individual biologic testing if at least 80% of patients receive results of biology studies within two weeks of study enrollment.
It will be considered feasible to treat patients based on biologic testing if at least and 50% of patients who consent for biology testing start therapy with one of four regimens within four weeks of study enrollment.
Measured: 3 years
Secondary outcomes (3)
Efficacy
Efficacy endpoint for patients with evaluable or measurable disease will be best objective response (CR, PR, SD or PD) measured by MRI imaging.
Measured: 3 years
Survival
Survival endpoints will be estimated including time to progression as well as progression-free and overall survival rates at the 6 month, 1 year and 2 year time point from start of study treatment.
Measured: 3 years
Toxicity
Toxicity endpoints will be descriptive and include grading of patient toxicity according to the National Cancer Institute common terminology criteria for adverse events (CTCAE version 4.0). This study is not intended or powered to compare toxicity between treatment arms. The tolerability of selected therapy with the addition of a kinase inhibitor will be described for all patients as a group.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2013 (estimated)
- Study startDec 2013
- Primary completionNov 2016
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Childhood Brain TumorStudies of the same condition, open and under way.
- More trials run by Seattle Children's HospitalThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seattle Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Cures Within Reach
- Responsible party
- Principal investigator, Sarah Leary, Seattle Children's Hospital
- Investigators
- Sarah ES Leary, MD, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02015728
- Sponsor's protocol ID
- SC-9006
- Acronym
- SEED
- Status last verified
- Dec 2016
- First submitted
- 13 Dec 2013
- Last updated
- 15 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Feasibility of Selecting Patient-Specific Biologically Targeted Therapy With Sorafenib, Everolimus, Erlotinib or Dasatinib for Pediatric Patients With Refractory Or Recurrent Brain Tumors
- ClinicalTrials.gov ID
- NCT02015728
- Acronym / sponsor ID
- SEED / SC-9006
- Conditions
- Recurrent Childhood Brain Tumor
- Keywords
- Refractory, Recurrent, Brain, Tumor, Pediatric, Biologically Targeted Therapy, Sorafenib, Everolimus
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Collaborators
- Cures Within Reach
- Study start
- Dec 2013
- Primary completion
- Nov 2016 (actual)
- Study completion
- Dec 2017 (estimated)
- First posted
- 19 Dec 2013 (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 research study is a Feasibility clinical trial. In this trial, researchers are trying to figure out whether a medication can be chosen based on rapid testing done on tumor tissue. Information from a feasibility or pilot trial will hopefully help researchers plan larger trials in the future to determine the effect of this therapy.
Detailed description
This research study will assign a specific drug treatment based on lab tests performed on the participant's tumor from tumor tissue taken from a biopsy done when he/she was first diagnosed or if taken when he/she relapsed or progressed. All participants will get Temozolomide and Etoposide to start. Then depending on review of the participant's tumor tissue he/she will also receive one of the following: Sorafenib, Everolimus, Erlotinib, or Dasatinib.
The purpose of this research study is to learn about the feasibility of obtaining and using information from studies done on tumor tissue in order to help make treatment decisions for patients with relapsed or refractory pediatric brain tumors. The investigators also want to find out the effects this therapy has on the participant and the participant's brain tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Regimen B | Experimental | Device: Tumor biology testing, Drug: Temozolomide, Drug: Etoposide, Drug: EverolimusDepending on tumor biology testing, subjects assigned to Regimen B will receive: Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Everolimus 3 mg/m2/dose daily PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. |
| Regimen C | Experimental | Device: Tumor biology testing, Drug: Temozolomide, Drug: Etoposide, Drug: ErlotinibDepending on tumor biology testing, subjects assigned to Regimen C will receive: Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Erlotinib 85 mg/m2/dose daily PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. |
| Regimen D | Experimental | Device: Tumor biology testing, Drug: Temozolomide, Drug: Etoposide, Drug: DasatinibDepending on tumor biology testing, subjects assigned to Regimen D will receive: Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Dasatinib 60 mg/m2/dose BID PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. |
| Regimen A | Experimental | Device: Tumor biology testing, Drug: Temozolomide, Drug: Etoposide, Drug: SorafenibDepending on tumor biology testing, subjects assigned to Regimen A will receive: Temozolomide 150 mg/m2/dose daily PO on days 1-5, Etoposide 50 mg/m2/dose daily PO on days 1-12, and Sorafenib 150 mg/m2/dose BID PO on days 1-28. Cycles will be repeated every 28 days for up to 12 cycles. |
Who may qualify
- Ages
- 1 month to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (24 listed)
- Patients must have histological confirmation of a brain tumor at diagnosis or relapse for all tumors.
- There must be documented progression or recurrence of disease by MRI imaging or CSF studies since completion of last tumor-directed medical therapy. Patients may have had surgical resection or radiation of tumor, and need not have measurable or evaluable disease at study entry.
- Patient's current disease state must be one for which there is no known curative therapy.
- Age greater than 1 month and less than 30 years at the time of enrollment.
- BSA greater than 0.3 m2 at the time of enrollment.
Key exclusion criteria (9 listed)
- Patients who are breastfeeding, pregnant or refuse to use an effective form of birth control are excluded. Abstinence is considered an effective form of birth control.
- Patients with uncontrolled infection are excluded.
- Patients with known bleeding disorders or more than punctate intratumoral hemorrhage are excluded.
- Patients receiving other anti-neoplastic agents are excluded.
- Patients on enzyme-inducing anticonvulsive agents 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 |
|---|---|---|
| Tumor biology testingAlso: IHC Testing, Immunohistochemical Screening, Immunohistochemical Test, Tumor MarkersTumor biology studies will be performed in a CLIA-approved clinical pathology laboratory using standard procedures. Immunohistochemical (IHC) testing will be performed on formalin fixed tumor obtained at the time of diagnosis and/or relapse. Results will be interpreted by a qualified pediatric pathologist and will be scored on a scale of 0 to 4+ commenting on both percentage of positive cells and intensity of staining. Results will further be reported as a binary result (positive/negative). If more than one tumor specimen is available from different surgical procedures (e.g. initial diagnosis and relapse), the results from the relapse specimen will be prioritized. Results will determine kinase inhibitor treatment arm assignment which will be administered in addition to the "best available" combination of low-dose oral cytotoxic agents, including temozolomide and etoposide. | Device | Regimen A, Regimen B, Regimen C, Regimen D |
| TemozolomideAlso: Temodar, Temodal, TemcadTemozolomide combined with Etoposide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors. | Drug | Regimen A, Regimen B, Regimen C, Regimen D |
| EtoposideAlso: Etopophos, VepesidEtoposide combined with Temozolomide is considered the "best available" combination of low-dose oral cytotoxic agents for patients with refractory or recurrent CNS tumors. | Drug | Regimen A, Regimen B, Regimen C, Regimen D |
| SorafenibAlso: NexavarSorafenib is a broad-spectrum kinase inhibitor. | Drug | Regimen A |
| EverolimusAlso: Zortress, CerticanEverolimus is an mTOR pathway inhibitor. | Drug | Regimen B |
| ErlotinibAlso: TarcevaErlotinib is a tyrosine kinase inhibitor of the ERBB family of proteins. | Drug | Regimen C |
| DasatinibAlso: SprycelDasatinib is a broad spectrum SRC inhibitor. | Drug | Regimen D |
Primary outcome
Feasibility
Time frame: 3 years
It will be considered feasible to obtain individual biologic testing if at least 80% of patients receive results of biology studies within two weeks of study enrollment. It will be considered feasible to treat patients based on biologic testing if at least and 50% of patients who consent for biology testing start therapy with one of four regimens within four weeks of study enrollment.
3 secondary outcomes
Efficacy
Time frame: 3 years
Survival
Time frame: 3 years
Toxicity
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 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.
Sarah ES Leary, MD principal investigator
Seattle 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 study testing Tumor biology testing, Temozolomide and Etoposide in people with Recurrent Childhood Brain Tumor, run by Seattle 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 24 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 15 Dec 2016. 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.
Are results available for this study?
Results are not available in the source record.
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?
Feasibility (time frame: 3 years). 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 15 Dec 2016.