neurofibromatosis1 (NF1)Phase 2NCT01338857
Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas
A Phase 2 study testing Sorafenib (Nexavar) in people with neurofibromatosis1 (NF1) and Recurrent or Progressive Optic Pathway Gliomas (OPG), run by NYU Langone Health at 1 site in United States.
Trial summary
The purpose of this study is to determine if a drug called sorafenib can shrink LGA tumors (low-grade astrocytomas) in children and adults. Previous research has given us a better understanding of this type of tumor by studying the genetic "make-up" of LGAs. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- neurofibromatosis1 (NF1), Recurrent or Progressive Optic Pathway Gliomas (OPG), Recurrent or Progressive Low-grade Glioma
- What is being tested?
- Sorafenib (Nexavar)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Mar 2013
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age: greater than or equal to 2 years of age
- Patients with neurofibromatosis-1 (NF1) are eligible
- Recurrent/progressive optic pathway gliomas (OPG) by MRI criteria, after standard therapy - histologic confirmation not required OR Histologically confirmed, radiographically recurrent or progressive low-grade glioma (WHO grade I or II) by MRI criteria, after standard therapy.
- Karnofsky performance status (PS) 60-100% (greater than or equal to 16 years of age) OR Lansky PS 60-100% (< 16 years of age)
- Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
- Platelet count ≥ 75,000/mm³ (unsupported)
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- Normal PT, PTT, and INR (for patients on prophylactic anticoagulation only)
- Diastolic blood pressure (DBP) ≤ the 95th percentile for age and gender and not currently receiving medication for the treatment of hypertension.
- Adequate pulmonary function, defined as: no evidence of dyspnea at rest, no exercise intolerance, and pulse oximetry > 94% if termination is clinically indicated.
- Not received myelosuppressive chemotherapy or treatment with biologicals or monoclonal antibodies within 4 weeks of enrollment onto this study (6 weeks if prior nitrosurea)
- At least 7 days since the completion of therapy with a hematopoietic growth factor and at least 14 days from the last administration of PEGylated GCSF (Neulasta®)
- If prior radiation therapy, ≥ 6 months must have elapsed since the last fraction for craniospinal therapy and ≥ 3 months for focal radiotherapy including radiosurgery.
- If prior surgery, ≥ 8 weeks must have elapsed since (≥ 4 weeks for minor surgery/procedures including central line placement)
- Steroids are allowed for progressive symptoms but patient must be on a stable or decreasing dose for at least 1 week prior to study entry
- Any neurologic deficits must be stable for ≥ 1 week
Who cannot join
- Patients with serious concurrent infection or medical illness, including overt hepatic or renal disease, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
- Baseline hypertension greater than grade 1.
- Prior treatment with sorafenib
- Other concurrent investigational drugs
- Other concurrent anticancer agents or therapies, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
- Concurrent therapeutic anticoagulation. Prophylactic anticoagulation (i.e. low dose heparin) of venous or arterial access devices is allowed.
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- Concurrent administration of any of cytochrome P450 enzyme-inducing agents, including grapefruit juice and drugs listed under Section 9.7.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection
- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event
- Any other hemorrhage/bleeding event
- Serious non-healing wound, ulcer, or bone fracture.
- Evidence or history of unresolved bleeding diathesis or coagulopathy.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
- Known or suspected allergy to sorafenib.
- Any malabsorption problem.
- Patients with history of any prior CNS bleeding.
- Patients with any non-healed wounds.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University Stephen D. Hassenfeld Children's Center for Cancer & Blood Disorders
New York, New York, 10016
About this study
Official title: Phase II Study of Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas
The purpose of this study is to determine if a drug called sorafenib can shrink LGA tumors (low-grade astrocytomas) in children and adults. Previous research has given us a better understanding of this type of tumor by studying the genetic "make-up" of LGAs. From this research, the investigators found that a drug called sorafenib may stop the growth of tumor cells by blocking some of the molecules needed for cell growth and by blocking blood flow to the tumor. This trial is studying how well sorafenib works in treating patients with LGAs, and how the effects relate to the specific genetic "make-up" of your particular tumor. This testing of your tumor's genetic make-up is optional and requires available tumor tissue for testing. In summary, the aims of this study are: To see if sorafenib can shrink LGAs; how well sorafenib is tolerated in patients with LGAs; and, how the effects of sorafenib relate to the genetic make-up of individual LGAs (Optional Study)
Read the detailed description
Novel therapies are urgently needed for children with relapsed LGA who are not surgical candidates and/or have exhausted standard chemotherapy approaches. Although a vast number of "molecular targeted" agents have been developed over the past decade for the treatment of cancer, none have been evaluated for the treatment of LGAs. Recently, genetic alterations resulting in oncogenic BRAF have been identified to be highly prevalent in LGAs, providing a rational target for therapeutic intervention.
The aims of this clinical trial are to estimate the efficacy, as well as safety and tolerability of sorafenib, a RAF and tyrosine kinase receptor inhibitor, in the treatment of pediatric patients with recurrent LGA. Sorafenib targets several pathways that, based on preliminary data from us and others, are likely contributing to the growth of LGAs: oncogenic BRAF, which is present in the majority of grade I LGAs and VEGFR2 and PDGFR, which are well-described mediators of tumor angiogenesis. Since sorafenib inhibits a number of additional kinases whose role in LGA growth has not yet been explored, it is possible that inhibition of pathways other than the primary targets may result in additional anti-tumor effects of sorafenib in LGA. Although the investigators hypothesize that LGAs with oncogenic BRAF should be most sensitive to sorafenib, the additional targets of sorafenib may also result in significant anti-tumor effects in LGAs with wild-type BRAF. Therefore, the investigators propose to evaluate the efficacy of sorafenib in children with LGAs in a translational clinical trial, stratified by BRAF status and tumor grade.
The investigators expect to learn the following from this clinical translational trial:
- The anti-tumor activity of sorafenib in pediatric LGAs
- The safety and tolerability of sorafenib in pediatric patients with LGAs
- The association of molecular target expression, e.g. oncogenic BRAF, with response rates
The investigators will use the results of the clinical translational trial to determine if sorafenib warrants further clinical study in pediatric LGAs. If the investigators find associations between molecular target expression and response, further studies may be limited to or focus on patients whose tumors have specific molecular features, such as oncogenic BRAF. Sorafenib has also shown promise in combination with classic chemotherapy and can be given together with carboplatin, which is one of the most active agents in LGAs. Therefore, possible synergy between sorafenib and traditional chemotherapy used in the treatment of LGAs, such as carboplatin, could be explored in future clinical trials.
- Conditions
- neurofibromatosis1 (NF1), Recurrent or Progressive Optic Pathway Gliomas (OPG), Recurrent or Progressive Low-grade Glioma
- Being tested
- Sorafenib (Nexavar)
- Keywords
- neurofibromatosis1 (NF1), Recurrent or progressive optic pathway gliomas (OPG), Recurrent or progressive low-grade glioma, sorafenib, low-grade astrocytoma
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib (Nexavar)Drug
Sorafenib (in tablet form) will be administered orally BID (approximately every 12 hours). Grapefruit juice is not allowed while taking sorafenib. A cycle of therapy is considered to be 28 days and there is no interruption between cycles. Patients may receive up to a total of 12 cycles provided that no off-protocol or off-study criteria are met.
Children/adolescents (< 18 years of age, non-NF1): 200 mg/m2/dose PO twice daily (rounded to the nearest 50 mg increment as per Section 4.1) to a maximum of 400 mg PO twice daily
Adults (greater than or equal to 18 years of age, non-NF1): 400 mg PO twice daily
NF1 patients (regardless of age): 80 mg/m2/dose PO twice daily (rounded to the nearest 50 mg increment as per Section 4.1) to a maximum of 150 mg PO twice daily
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib (Nexavar) | Experimental | Sorafenib will be administered orally BID (approximately every 12 hours). Grapefruit juice is not allowed while taking sorafenib. A cycle of therapy is considered to be 28 days and there is no interruption between cycles. Patients may receive up to a total of 12 cycles provided that no off-protocol or off-study criteria are met. Receives: Drug: Sorafenib (Nexavar) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate to Sorafenib
To estimate the objective response rates to sorafenib in children and young adults with low-grade astrocytomas, including optic pathway gliomas.
Measured: one year
Objective Response Rates
Determination of tumor response (CR, PR, SD) will be defined based on the comparison of the baseline MRI performed at study entry to the subsequent MRI which demonstrated best response. PR will be defined by a >15% decrease in tumor volume, as measured by 3D volumetric analysis.
Measured: MRIs performed after every 3rd 28-day cycle and off-study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2011 (estimated)
- Study startApr 2011
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: Sorafenib ineffective for tx of recurrent or progressive PLGA
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 neurofibromatosis1 (NF1)Studies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Responsible party
- Sponsor
- Investigators
- Matthias A Karajannis, MD, Principal investigator, NYU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01338857
- Sponsor's protocol ID
- 10-00561
- Status last verified
- Dec 2016
- First submitted
- 18 Apr 2011
- Last updated
- 17 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Legault G, Kieran MW, Scott RM, Chordas C, Milla SS, Karajannis MA. Recurrent ascites in a patient with low-grade astrocytoma and ventriculo-peritoneal shunt treated with the multikinase inhibitor sorafenib. J Pediatr Hematol Oncol. 2014 Nov;36(8):e533-5. doi: 10.1097/MPH.0000000000000094.
PubMed 24351969
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Sorafenib in Children and Young Adults With Recurrent or Progressive Low-Grade Astrocytomas
- ClinicalTrials.gov ID
- NCT01338857
- Acronym / sponsor ID
- 10-00561
- Conditions
- neurofibromatosis1 (NF1), Recurrent or Progressive Optic Pathway Gliomas (OPG), Recurrent or Progressive Low-grade Glioma
- Keywords
- neurofibromatosis1 (NF1), Recurrent or progressive optic pathway gliomas (OPG), Recurrent or progressive low-grade glioma, sorafenib, low-grade astrocytoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sorafenib ineffective for tx of recurrent or progressive PLGA
- Enrolment
- 12 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
- Study start
- Apr 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 20 Apr 2011 (estimated)
- Results
- Posted 22 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if a drug called sorafenib can shrink LGA tumors (low-grade astrocytomas) in children and adults. Previous research has given us a better understanding of this type of tumor by studying the genetic "make-up" of LGAs. From this research, the investigators found that a drug called sorafenib may stop the growth of tumor cells by blocking some of the molecules needed for cell growth and by blocking blood flow to the tumor. This trial is studying how well sorafenib works in treating patients with LGAs, and how the effects relate to the specific genetic "make-up" of your particular tumor. This testing of your tumor's genetic make-up is optional and requires available tumor tissue for testing. In summary, the aims of this study are: To see if sorafenib can shrink LGAs; how well sorafenib is tolerated in patients with LGAs; and, how the effects of sorafenib relate to the genetic make-up of individual LGAs (Optional Study)
Detailed description
Novel therapies are urgently needed for children with relapsed LGA who are not surgical candidates and/or have exhausted standard chemotherapy approaches. Although a vast number of "molecular targeted" agents have been developed over the past decade for the treatment of cancer, none have been evaluated for the treatment of LGAs. Recently, genetic alterations resulting in oncogenic BRAF have been identified to be highly prevalent in LGAs, providing a rational target for therapeutic intervention.
The aims of this clinical trial are to estimate the efficacy, as well as safety and tolerability of sorafenib, a RAF and tyrosine kinase receptor inhibitor, in the treatment of pediatric patients with recurrent LGA. Sorafenib targets several pathways that, based on preliminary data from us and others, are likely contributing to the growth of LGAs: oncogenic BRAF, which is present in the majority of grade I LGAs and VEGFR2 and PDGFR, which are well-described mediators of tumor angiogenesis. Since sorafenib inhibits a number of additional kinases whose role in LGA growth has not yet been explored, it is possible that inhibition of pathways other than the primary targets may result in additional anti-tumor effects of sorafenib in LGA. Although the investigators hypothesize that LGAs with oncogenic BRAF should be most sensitive to sorafenib, the additional targets of sorafenib may also result in significant anti-tumor effects in LGAs with wild-type BRAF. Therefore, the investigators propose to evaluate the efficacy of sorafenib in children with LGAs in a translational clinical trial, stratified by BRAF status and tumor grade.
The investigators expect to learn the following from this clinical translational trial:
- The anti-tumor activity of sorafenib in pediatric LGAs
- The safety and tolerability of sorafenib in pediatric patients with LGAs
- The association of molecular target expression, e.g. oncogenic BRAF, with response rates
The investigators will use the results of the clinical translational trial to determine if sorafenib warrants further clinical study in pediatric LGAs. If the investigators find associations between molecular target expression and response, further studies may be limited to or focus on patients whose tumors have specific molecular features, such as oncogenic BRAF. Sorafenib has also shown promise in combination with classic chemotherapy and can be given together with carboplatin, which is one of the most active agents in LGAs. Therefore, possible synergy between sorafenib and traditional chemotherapy used in the treatment of LGAs, such as carboplatin, could be explored in future clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib (Nexavar) | Experimental | Drug: Sorafenib (Nexavar)Sorafenib will be administered orally BID (approximately every 12 hours). Grapefruit juice is not allowed while taking sorafenib. A cycle of therapy is considered to be 28 days and there is no interruption between cycles. Patients may receive up to a total of 12 cycles provided that no off-protocol or off-study criteria are met. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Age: greater than or equal to 2 years of age
- Patients with neurofibromatosis-1 (NF1) are eligible
- Recurrent/progressive optic pathway gliomas (OPG) by MRI criteria, after standard therapy - histologic confirmation not required OR Histologically confirmed, radiographically recurrent or progressive low-grade glioma (WHO grade I or II) by MRI criteria, after standard therapy.
- Karnofsky performance status (PS) 60-100% (greater than or equal to 16 years of age) OR Lansky PS 60-100% (< 16 years of age)
- Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
Key exclusion criteria (20 listed)
- Patients with serious concurrent infection or medical illness, including overt hepatic or renal disease, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
- Baseline hypertension greater than grade 1.
- Prior treatment with sorafenib
- Other concurrent investigational drugs
- Other concurrent anticancer agents or therapies, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
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 |
|---|---|---|
| Sorafenib (Nexavar)Sorafenib (in tablet form) will be administered orally BID (approximately every 12 hours). Grapefruit juice is not allowed while taking sorafenib. A cycle of therapy is considered to be 28 days and there is no interruption between cycles. Patients may receive up to a total of 12 cycles provided that no off-protocol or off-study criteria are met. Children/adolescents (< 18 years of age, non-NF1): 200 mg/m2/dose PO twice daily (rounded to the nearest 50 mg increment as per Section 4.1) to a maximum of 400 mg PO twice daily Adults (greater than or equal to 18 years of age, non-NF1): 400 mg PO twice daily NF1 patients (regardless of age): 80 mg/m2/dose PO twice daily (rounded to the nearest 50 mg increment as per Section 4.1) to a maximum of 150 mg PO twice daily | Drug | Sorafenib (Nexavar) |
Primary outcome
Response Rate to Sorafenib
Time frame: one year
To estimate the objective response rates to sorafenib in children and young adults with low-grade astrocytomas, including optic pathway gliomas.
Objective Response Rates
Time frame: MRIs performed after every 3rd 28-day cycle and off-study
Determination of tumor response (CR, PR, SD) will be defined based on the comparison of the baseline MRI performed at study entry to the subsequent MRI which demonstrated best response. PR will be defined by a >15% decrease in tumor volume, as measured by 3D volumetric analysis.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24351969Legault G, Kieran MW, Scott RM, Chordas C, Milla SS, Karajannis MA. Recurrent ascites in a patient with low-grade astrocytoma and ventriculo-peritoneal shunt treated with the multikinase inhibitor sorafenib. J Pediatr Hematol Oncol. 2014 Nov;36(8):e533-5. doi: 10.1097/MPH.0000000000000094.
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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.
Matthias A Karajannis, MD principal investigator
NYU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib (Nexavar) in people with neurofibromatosis1 (NF1) and Recurrent or Progressive Optic Pathway Gliomas (OPG), run by NYU Langone Health 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 15 inclusion and 20 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: stopped early, as of the sponsor's last update on 17 Feb 2017. 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 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 22 Feb 2016). 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?
Response Rate to Sorafenib (time frame: one year). The study lists 2 primary outcomes in all. 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 NCT01338857, 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 17 Feb 2017.