SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01217437

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Temozolomide With Irinotecan Versus Temozolomide, Irinotecan Plus Bevacizumab (NSC# 704865) for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, a COG Randomized Phase II Screening Trial

This randomized phase II trial studies how well giving temozolomide and irinotecan hydrochloride together with or without bevacizumab works in treating young patients with recurrent or refractory medulloblastoma or central nervous system (CNS) primitive neuroectodermal tumors. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide and irinotecan hydrochloride are more effective with or without bevacizumab in treating medulloblastoma or CNS primitive neuroectodermal tumors.

NCT01217437 Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified
MeSH: Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Pinealoma
HPO: Ependymoblastoma Medulloblastoma Medulloepithelioma Neuroectodermal neoplasm Pineal parenchymal cell neoplasm Pinealoma Pineoblastoma Pineocytoma Primitive neuroectodermal tumor Supratentorial neoplasm

3 Interventions

Name: Bevacizumab

Description: Given IV

Type: Biological

Arm II (temozolomide, irinotecan hydrochloride, bevacizumab)

Name: Irinotecan Hydrochloride

Description: Given IV

Type: Drug

Arm I (temozolomide, irinotecan hydrochloride) Arm II (temozolomide, irinotecan hydrochloride, bevacizumab)

Name: Temozolomide

Description: Given PO

Type: Drug

Arm I (temozolomide, irinotecan hydrochloride) Arm II (temozolomide, irinotecan hydrochloride, bevacizumab)


Primary Outcomes

Description: Estimated by Kaplan-Meier method to aggregate the overall survival for each patient.

Measure: Overall survival for each treatment arm

Time: Up to 5 years

Secondary Outcomes

Description: Estimated assuming a binomial response model.

Measure: Response rate for each treatment arm

Time: Up to 5 years

Description: Estimated by Kaplan-Meier method to aggregate the overall survival for each patient.

Measure: Event-free survival

Time: From enrollment to disease progression, second malignant neoplasm, death regardless of cause, or date of last contact, whichever comes first, up to 5 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 G20210A

Estimated by Kaplan-Meier method to aggregate the overall survival for each patient.. Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Pinealoma PRIMARY OBJECTIVES: l. --- G20210A ---

Estimated by Kaplan-Meier method to aggregate the overall survival for each patient.. Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Pinealoma PRIMARY OBJECTIVES: l. --- G20210A --- --- G20210A ---



HPO Nodes


HPO:
Ependymoblastoma
Medulloblastoma
Genes 14
PTCH2 APC SUFU MLH1 SMARCB1 NBN MSH6 DICER1 PALB2 PMS2 MSH2 KEAP1 CTNNB1 PTCH1
Medulloepithelioma
Genes 2
KEAP1 DICER1
Neuroectodermal neoplasm
Genes 61
PMS1 GABRD CDKN2A NUTM1 KRAS RAF1 TGFBR2 FLI1 MSH6 ERBB2 BMPR1A PMS2 PTPN11 MLH3 IGF2 NF1 GPC3 BRAF NF2 RB1 PIK3CA ASCL1 MYO1H BRD4 SETBP1 GPC4 TUBB CHEK2 KCNAB2 APC MLH1 LRP5 NBN C11ORF95 RPS20 TSC1 TSC2 RELA MSH2 MSH3 RERE KEAP1 IDH1 IDH2 SEMA4A RET RUNX1 NME1 PHOX2B SKI MAPRE2 EPCAM PRDM16 GDNF DICER1 PALB2 BDNF EDN3 H19 SDHB FAN1
Pineal parenchymal cell neoplasm
Pinealoma
Genes 1
RB1
Pineoblastoma
Pineocytoma
Primitive neuroectodermal tumor
Genes 43
KCNAB2 PMS1 GABRD MLH1 NUTM1 KRAS RAF1 TGFBR2 FLI1 MSH6 RPS20 BMPR1A PMS2 MSH2 PTPN11 MLH3 RERE KEAP1 SEMA4A NF1 RET RUNX1 NME1 GPC3 BRAF PHOX2B SKI MAPRE2 EPCAM PRDM16 PIK3CA GDNF ASCL1 DICER1 PALB2 MYO1H BDNF EDN3 BRD4 SDHB FAN1 GPC4 TUBB
Supratentorial neoplasm
Genes 3
RELA RB1 C11ORF95