Diffuse Intrinsic Pontine GliomaPhase 2NCT01182350
Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)
A Phase 2 study testing Bevacizumab, Erlotinib and Temozolomide in people with Diffuse Intrinsic Pontine Glioma, run by Karen D. Wright MD at 23 sites in United States.
Trial summary
Diagnosis of diffuse intrinsic pontine glioma (DIPG) for decades has relied on imaging studies and clinical findings. Histologic confirmation has been absent with surgical biopsy of brainstem tumors not believed to have acceptable safety. Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Bevacizumab, Erlotinib and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 23 sitesUnited States
- Study dates
- Sep 2011to Jun 2016
- 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 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Tumor: Newly diagnosed non-disseminated diffuse intrinsic pontine glioma based on classic clinical AND radiographic finding.
- No prior radiation therapy or chemotherapy.
- Age: Patient must be 3 to < 18 years of age at the time of diagnosis.
- Performance Score: Karnofsky Performance Scale > 12 y/o >/= 50 or Lansky Performance Score for patients < 12y/o 50 assessed within two-weeks prior to enrollment.
- Participants must have normal organ and marrow function as defined below within two week s prior to enrollment:
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- Absolute neutrophil count > 1,000/mcL
- Platelets > 100,000/mcL (transfusion independent)
- Hemoglobin > 8gm/dL (can be transfused)
- Hepatic: Total bilirubin < 1.5 times the upper limit of normal; alanine aminotransferase [SGPT (ALT)] and aspartate aminotransferase [SGOT (AST)] < 5 times the institutional upper limit of normal.
- Renal: Serum creatinine which is less than 1.5x the upper limit of institutional normal for age or Glomerular Filtration Rate (GFR) > 70 ml/min/1.73m2.
- Female patients of childbearing potential must have negative serum or urine pregnancy test. Patient must not be pregnant or breast feeding.
- Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Patients receiving any other anticancer or experimental drug therapy.
- Patients with disseminated intrinsic diffuse brainstem gliomas in either brain or spine (can be based on clinical evaluation).
- Participants receiving any medications or substances that are strong/intermediate inhibitors or inducers of Cytochrome P450 (CYP450), Cytochrome P3A4(CYP3A4) or Cytochrome 1A2 (CYP1A2) are ineligible. Lists including medications and substances known or with the potential to interact with the CYP450 CYP3A4 or CYP1A2 isoenzymes are provided in Appendix I.
- Use of hematopoietic growth factors within the 2 weeks prior to initiation of therapy.
- Patients with evidence of spontaneous hemorrhage greater than 0.5cm unrelated to surgery.
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- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bevacizumab, temozolomide and erlotinib can have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued.
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Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins
Baltimore, Maryland, 21287
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Medical University of South Carolina
Charleston, South Carolina, 29425
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
UT Southwestern Medical Center
Dallas, Texas, 75390
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke University
Durham, North Carolina, 27710
Cook Children's Medical Center
Fort Worth, Texas, 76104
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
Nemours Children's Clinic
Jacksonville, Florida, 32207
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of Louisville
Louisville, Kentucky, 40202
Miami Children's Hospital
Miami, Florida, 33155
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
New York University
New York, New York, 10016
Stanford University/Lucile Packard Children's Hospital
Palo Alto, California, 94304
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Doernbecher Children's Hospital
Portland, Oregon, 97239
University of California, San Francisco
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University Medical Center
St Louis, Missouri, 63110
About this study
Official title: Phase II Trial of Molecularly Determined Treatment of Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas
Diagnosis of diffuse intrinsic pontine glioma (DIPG) for decades has relied on imaging studies and clinical findings. Histologic confirmation has been absent with surgical biopsy of brainstem tumors not believed to have acceptable safety. The prognosis of DIPG has remained quite poor and novel therapeutic strategies are needed. This DIPG Biology and Treatment Study (DIPG-BATS) study incorporates a surgical biopsy at presentation using strict preoperative neurosurgical planning and stratifies participants to receive FDA-approved agents chosen on the basis of specific biologic targets. This is the first prospective national clinical trial to examine the feasibility and safety of incorporating surgical biopsy into potential treatment strategies for children with DIPG.
Read the detailed description
The primary objective of this study is to estimate the overall survival of children and young adults with DIPG in the context of a molecularly based treatment strategy, compared to historical controls (COG ACNS0126). Secondary objectives were to determine the safety and potential morbidity associated with biopsy of classic DIPGs based on imaging and clinical history as well as ability to perform biologic analyses on the biopsy material obtained to guide therapy. At study entry, a MRI-guided frameless or frame-based stereotactic biopsy will be performed approaching the pontine termentum through a trans-cerebellar or trans-frontal route. The exact biopsy location will be determined by the treating neurosurgeon at the designated participating site with the goal of minimizing procedural risk. Treatment directed based on tumor biopsy results requires classification of patients into 1 of 4 potential cohorts: O^6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status (negative versus positive) and epidermal growth factor receptor (EGFR) overexpression status (negative versus positive).
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Being tested
- Bevacizumab, Erlotinib, Temozolomide, Radiation
- Keywords
- Molecularly Determined Treatment
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
ErlotinibDrug
Also called Tarceva
TemozolomideDrug
Also called Temodar
RadiationRadiation
Also called irradiation
| Study group | Role | What they receive |
|---|---|---|
| radiation + bevacizumab | Experimental | Cohort 1: MGMT-/EGFR-
Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days).
Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy
Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles Receives: Drug: Bevacizumab; Radiation: Radiation |
| radiation + bevacizumab + erlotinib | Experimental | Cohort 2: MGMT-/EGFR+
Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days).
Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy
Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles
Erlotinib: Administered orally at 85 mg/m2 daily continuously during radiation therapy, through the interim period and for up to 10 maintenance cycles Receives: Drug: Bevacizumab; Drug: Erlotinib |
| radiation + bevacizumab + temozolomide | Experimental | Cohort 3. MGMT+/EGFR-
Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days).
Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy
Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles
Temozolomide: Administered orally at 90 mg/m2/day continuously during radiation therapy, held through the interim period and then 200 mg/m2/day for 5 days for up to 10 maintenance cycles Receives: Drug: Bevacizumab; Drug: Temozolomide; Radiation: Radiation |
| radiation + bevacizumab + erlotinib + temozolomide | Experimental | Cohort 4. MGMT+/EGFR+
Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days).
Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy
Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles
Erlotinib: Administered orally at 85 mg/m2 daily continuously during radiation therapy, through the interim period and for up to 10 maintenance cycles Receives: Drug: Bevacizumab; Drug: Erlotinib; Drug: Temozolomide; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
9-month Overall Survival (OS) Rate
9-month overall survival is the percentage of participants remaining alive 9 months from registration.
Measured: 9 months
Secondary outcomes (6)
Rate of Lethal Complications From Surgery
The rate of lethal complications from surgery is the percentage of participants dying as a result of surgery.
Measured: 2 weeks
Grade 3-4 Post-Procedural Surgery-Related Toxicity Rate
Grade 3-4 post-procedural surgery-related toxicity rate is the percentage of participants experiencing at least one grade 3-4 adverse event (AE) during the post-procedural time frame of 14 days attributable to the surgical procedure based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4).
Measured: 2 weeks
Delay in Radiation Therapy Start
The number of participants delaying the start of radiation therapy by more than 3 weeks due to complications as a result of surgical biopsy to obtain diagnostic tumor sample.
Measured: 3 weeks
Feasibility Rate of Molecular Approach to Therapy
Feasibility rate of the molecular strategy is based on the percentage of participants either with inadequate tissue from surgical biopsy to confirm DIPG diagnosis and/or with uninterpretable results for identification of EGFR overexpression and MGMT methylation status.
Measured: 3 weeks
Number of Participants With Grade 3-4 Treatment-Related Toxicity Over Chemoradiation Therapy
Counts any participant experiencing at least one treatment-related grade 3 or 4 adverse event (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) over chemoradiation therapy as reported on case report forms.
Measured: Adverse events were routinely throughout treatment. Treatment duration was a median of 6.4 months (range 0.4-13.4 months) in this study cohort.
Median Progression Free Survival (PFS)
PFS based on the Kaplan-Meier method is defined as the duration of time [months (m)] from study entry to documented disease progression (PD) or death. Participants alive without PD are censored at the date of last disease assessment. For intrinsic pontine brainstem gliomas, only one lesion/mass is present at diagnosis. Comparisons of maximal 2-dimensional measurements, TxW (product of the longest diameter [width (W)] and its longest perpendicular diameter [transverse (T)]) are used to assess response for this target lesion. PD is 25% or more increase, taking as reference the smallest product observed since the start of treatment, or the appearance of one or more new lesions.
Measured: Disease assessments using a standard CNS imaging protocol occurred chemoradiation cycles 1 and 2, every other maintenance cycle, every 3 months post-treatment year 1 then annually until PD or therapy change; In this study cohort, follow-up was up to 34m.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2010 (estimated)
- Study startSep 2011
- Primary completionJun 2016
- Study completionJun 2016
Why it stopped: Per design: Stop if fewer than 3 cohorts by molecular classification were with 10 participants or only 1 cohort enrolled at least 15 participants of 50.
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 Diffuse Intrinsic Pontine GliomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is not a randomized trial rather participants are classified and therapy is directed based on molecular profile obtained from surgical biopsy.
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karen D. Wright MD
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital, University of California, San Francisco, Ann & Robert H Lurie Children's Hospital of Chicago, Children's Healthcare of Atlanta, Children's Hospital Colorado, Children's Hospital Los Angeles, Children's Hospital of Michigan, Children's Hospitals and Clinics of Minnesota, Cook Children's Medical Center, OHSU Doernbecher Children's Hospital, Duke University, Johns Hopkins University, Nicklaus Children's Hospital f/k/a Miami Children's Hospital, Nemours Children's Clinic, New York University, Milton S. Hershey Medical Center, Seattle Children's Hospital, Lucile Packard Children's Hospital, University of Louisville, Children's National Research Institute, Washington University School of Medicine, Phoenix Children's Hospital, Medical University of South Carolina
- Responsible party
- Sponsor-investigator, Karen D. Wright MD, Dana-Farber Cancer Institute
- Investigators
- Karen D. Wright, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01182350
- Sponsor's protocol ID
- DFCI 10-321
- Status last verified
- Aug 2019
- First submitted
- 12 Aug 2010
- Last updated
- 4 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Gupta N, Goumnerova LC, Manley P, Chi SN, Neuberg D, Puligandla M, Fangusaro J, Goldman S, Tomita T, Alden T, DiPatri A, Rubin JB, Gauvain K, Limbrick D, Leonard J, Geyer JR, Leary S, Browd S, Wang Z, Sood S, Bendel A, Nagib M, Gardner S, Karajannis MA, Harter D, Ayyanar K, Gump W, Bowers DC, Weprin B, MacDonald TJ, Aguilera D, Brahma B, Robison NJ, Kiehna E, Krieger M, Sandler E, Aldana P, Khatib Z, Ragheb J, Bhatia S, Mueller S, Banerjee A, Bredlau AL, Gururangan S, Fuchs H, Cohen KJ, Jallo G, Dorris K, Handler M, Comito M, Dias M, Nazemi K, Baird L, Murray J, Lindeman N, Hornick JL, Malkin H, Sinai C, Greenspan L, Wright KD, Prados M, Bandopadhayay P, Ligon KL, Kieran MW. Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma. Neuro Oncol. 2018 Oct 9;20(11):1547-1555. doi: 10.1093/neuonc/noy070.
PubMed 29741745
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Molecularly Determined Treatment of Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas
- ClinicalTrials.gov ID
- NCT01182350
- Acronym / sponsor ID
- DFCI 10-321
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Keywords
- Molecularly Determined Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Per design: Stop if fewer than 3 cohorts by molecular classification were with 10 participants or only 1 cohort enrolled at least 15 participants of 50.
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Karen D. Wright MDUniversity, hospital or other
- Collaborators
- Boston Children's Hospital, University of California, San Francisco, Ann & Robert H Lurie Children's Hospital of Chicago, Children's Healthcare of Atlanta, Children's Hospital Colorado, Children's Hospital Los Angeles, Children's Hospital of Michigan, Children's Hospitals and Clinics of Minnesota, Cook Children's Medical Center, OHSU Doernbecher Children's Hospital, Duke University, Johns Hopkins University, Nicklaus Children's Hospital f/k/a Miami Children's Hospital, Nemours Children's Clinic, New York University, Milton S. Hershey Medical Center, Seattle Children's Hospital, Lucile Packard Children's Hospital, University of Louisville, Children's National Research Institute, Washington University School of Medicine, Phoenix Children's Hospital, Medical University of South Carolina
- Study start
- Sep 2011 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 16 Aug 2010 (estimated)
- Results
- Posted 4 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diagnosis of diffuse intrinsic pontine glioma (DIPG) for decades has relied on imaging studies and clinical findings. Histologic confirmation has been absent with surgical biopsy of brainstem tumors not believed to have acceptable safety. The prognosis of DIPG has remained quite poor and novel therapeutic strategies are needed. This DIPG Biology and Treatment Study (DIPG-BATS) study incorporates a surgical biopsy at presentation using strict preoperative neurosurgical planning and stratifies participants to receive FDA-approved agents chosen on the basis of specific biologic targets. This is the first prospective national clinical trial to examine the feasibility and safety of incorporating surgical biopsy into potential treatment strategies for children with DIPG.
Detailed description
The primary objective of this study is to estimate the overall survival of children and young adults with DIPG in the context of a molecularly based treatment strategy, compared to historical controls (COG ACNS0126). Secondary objectives were to determine the safety and potential morbidity associated with biopsy of classic DIPGs based on imaging and clinical history as well as ability to perform biologic analyses on the biopsy material obtained to guide therapy. At study entry, a MRI-guided frameless or frame-based stereotactic biopsy will be performed approaching the pontine termentum through a trans-cerebellar or trans-frontal route. The exact biopsy location will be determined by the treating neurosurgeon at the designated participating site with the goal of minimizing procedural risk. Treatment directed based on tumor biopsy results requires classification of patients into 1 of 4 potential cohorts: O^6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status (negative versus positive) and epidermal growth factor receptor (EGFR) overexpression status (negative versus positive).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is not a randomized trial rather participants are classified and therapy is directed based on molecular profile obtained from surgical biopsy.
| Arm | Type | Receives |
|---|---|---|
| radiation + bevacizumab | Experimental | Drug: Bevacizumab, Radiation: RadiationCohort 1: MGMT-/EGFR- Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days). Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles |
| radiation + bevacizumab + erlotinib | Experimental | Drug: Bevacizumab, Drug: ErlotinibCohort 2: MGMT-/EGFR+ Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days). Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles Erlotinib: Administered orally at 85 mg/m2 daily continuously during radiation therapy, through the interim period and for up to 10 maintenance cycles |
| radiation + bevacizumab + temozolomide | Experimental | Drug: Bevacizumab, Drug: Temozolomide, Radiation: RadiationCohort 3. MGMT+/EGFR- Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days). Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles Temozolomide: Administered orally at 90 mg/m2/day continuously during radiation therapy, held through the interim period and then 200 mg/m2/day for 5 days for up to 10 maintenance cycles |
| radiation + bevacizumab + erlotinib + temozolomide | Experimental | Drug: Bevacizumab, Drug: Erlotinib, Drug: Temozolomide, Radiation: RadiationCohort 4. MGMT+/EGFR+ Protocol treatment lasts approximately 52 weeks including a 4-week interim period once radiation therapy is completed and a maintenance phase (cycle duration=28 days). Radiation therapy: Given in 180 cGy fractions to a total dose of 59.4 + 1.8 Gy/-5.4 Gy for approximately 7 weeks beginning 7-21 days after biopsy Bevacizumab: Administered intravenously at 10 mg/kg beginning no sooner than 21 days from biopsy and every 14 days concurrent with radiation therapy, through the interim period and for up to 10 maintenance cycles Erlotinib: Administered orally at 85 mg/m2 daily continuously during radiation therapy, through the interim period and for up to 10 maintenance cycles |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Tumor: Newly diagnosed non-disseminated diffuse intrinsic pontine glioma based on classic clinical AND radiographic finding.
- No prior radiation therapy or chemotherapy.
- Age: Patient must be 3 to < 18 years of age at the time of diagnosis.
- Performance Score: Karnofsky Performance Scale > 12 y/o >/= 50 or Lansky Performance Score for patients < 12y/o 50 assessed within two-weeks prior to enrollment.
Key exclusion criteria (9 listed)
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Patients receiving any other anticancer or experimental drug therapy.
- Patients with disseminated intrinsic diffuse brainstem gliomas in either brain or spine (can be based on clinical evaluation).
- Participants receiving any medications or substances that are strong/intermediate inhibitors or inducers of Cytochrome P450 (CYP450), Cytochrome P3A4(CYP3A4) or Cytochrome 1A2 (CYP1A2) are ineligible. Lists including medications and substances known or with the potential to interact with the CYP450 CYP3A4 or CYP1A2 isoenzymes are provided in Appendix I.
- Use of hematopoietic growth factors within the 2 weeks prior to initiation of 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 |
|---|---|---|
| BevacizumabAlso: Avastin | Drug | radiation + bevacizumab, radiation + bevacizumab + erlotinib, radiation + bevacizumab + erlotinib + temozolomide, radiation + bevacizumab + temozolomide |
| ErlotinibAlso: Tarceva | Drug | radiation + bevacizumab + erlotinib, radiation + bevacizumab + erlotinib + temozolomide |
| TemozolomideAlso: Temodar | Drug | radiation + bevacizumab + erlotinib + temozolomide, radiation + bevacizumab + temozolomide |
| RadiationAlso: irradiation | Radiation | radiation + bevacizumab, radiation + bevacizumab + erlotinib + temozolomide, radiation + bevacizumab + temozolomide |
Primary outcome
9-month Overall Survival (OS) Rate
Time frame: 9 months
9-month overall survival is the percentage of participants remaining alive 9 months from registration.
6 secondary outcomes
Rate of Lethal Complications From Surgery
Time frame: 2 weeks
Grade 3-4 Post-Procedural Surgery-Related Toxicity Rate
Time frame: 2 weeks
Delay in Radiation Therapy Start
Time frame: 3 weeks
Feasibility Rate of Molecular Approach to Therapy
Time frame: 3 weeks
Number of Participants With Grade 3-4 Treatment-Related Toxicity Over Chemoradiation Therapy
Time frame: Adverse events were routinely throughout treatment. Treatment duration was a median of 6.4 months (range 0.4-13.4 months) in this study cohort.
Median Progression Free Survival (PFS)
Time frame: Disease assessments using a standard CNS imaging protocol occurred chemoradiation cycles 1 and 2, every other maintenance cycle, every 3 months post-treatment year 1 then annually until PD or therapy change; In this study cohort, follow-up was up to 34m.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29741745Gupta N, Goumnerova LC, Manley P, Chi SN, Neuberg D, Puligandla M, Fangusaro J, Goldman S, Tomita T, Alden T, DiPatri A, Rubin JB, Gauvain K, Limbrick D, Leonard J, Geyer JR, Leary S, Browd S, Wang Z, Sood S, Bendel A, Nagib M, Gardner S, Karajannis MA, Harter D, Ayyanar K, Gump W, Bowers DC, Weprin B, MacDonald TJ, Aguilera D, Brahma B, Robison NJ, Kiehna E, Krieger M, Sandler E, Aldana P, Khatib Z, Ragheb J, Bhatia S, Mueller S, Banerjee A, Bredlau AL, Gururangan S, Fuchs H, Cohen KJ, Jallo G, Dorris K, Handler M, Comito M, Dias M, Nazemi K, Baird L, Murray J, Lindeman N, Hornick JL, Malkin H, Sinai C, Greenspan L, Wright KD, Prados M, Bandopadhayay P, Ligon KL, Kieran MW. Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma. Neuro Oncol. 2018 Oct 9;20(11):1547-1555. doi: 10.1093/neuonc/noy070.
- Individual participant dataSharing planned: No
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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.
Karen D. Wright, MD principal investigator
Dana-Farber Cancer Institute
23 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 Bevacizumab, Erlotinib and Temozolomide in people with Diffuse Intrinsic Pontine Glioma, run by Karen D. Wright MD at 23 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 14 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: stopped early, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 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 4 Sep 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?
9-month Overall Survival (OS) Rate (time frame: 9 months). 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 NCT01182350, 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 4 Sep 2019.