Brief Summary
This phase II trial studies how well combination chemotherapy works in treating younger patients with newly diagnosed, non-metastatic desmoplastic medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cyclophosphamide, methotrexate, etoposide, and carboplatin, 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.
Brief Title
Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma
Detailed Description
PRIMARY OBJECTIVES:
I. Estimate of the progression free survival (PFS) distribution for patients 0-\<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).
OTHER PRE-SPECIFIED OBJECTIVES:
I. Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.
II. Prospectively evaluate the molecular profile of nodular desmoplastic (ND)/medulloblastoma with extensive nodularity (MBEN) medulloblastoma in young children.
III. Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.
OUTLINE:
INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity.
CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 16, 20, 24, 36, 48, 60, and 72 months.
I. Estimate of the progression free survival (PFS) distribution for patients 0-\<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).
OTHER PRE-SPECIFIED OBJECTIVES:
I. Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.
II. Prospectively evaluate the molecular profile of nodular desmoplastic (ND)/medulloblastoma with extensive nodularity (MBEN) medulloblastoma in young children.
III. Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.
OUTLINE:
INDUCTION THERAPY: Patients receive vincristine sulfate intravenously (IV) over 1 minute or infused via minibag on days 1, 15, and 29; cyclophosphamide IV over 1 hour on days 1-3; methotrexate IV over 24 hours on days 15 and 29; etoposide IV over 60-120 minutes on days 43-45; and carboplatin IV over 1 hour on days 43-45. Treatment repeats every 63 days for 3 courses in the absence of disease progression or unacceptable toxicity.
CONTINUATION THERAPY: Patients receive vincristine sulfate IV over 1 minute or infused via minibag on day 1, cyclophosphamide IV over 1 hour on days 1-3, etoposide IV over 60-120 minutes on days 21-23, and carboplatin IV over 1 hour on days 21-23. Treatment repeats every 42 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 16, 20, 24, 36, 48, 60, and 72 months.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Desmoplastic/Nodular Medulloblastoma
Medulloblastoma
Medulloblastoma With Extensive Nodularity
Nevoid Basal Cell Carcinoma Syndrome
Eligibility Criteria
Inclusion Criteria:
* Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
* Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
* Patients must have:
* Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)
* Post-operative cranial MRI with and without gadolinium within 72 hours of surgery
* Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery
* Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent)
* Hemoglobin \>= 10.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* 1 month to \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status, coma or assisted ventilation prior to study enrollment
Exclusion Criteria:
* Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible
* Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids
* Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
* Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
* Patients must have:
* Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)
* Post-operative cranial MRI with and without gadolinium within 72 hours of surgery
* Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery
* Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent)
* Hemoglobin \>= 10.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* 1 month to \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status, coma or assisted ventilation prior to study enrollment
Exclusion Criteria:
* Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible
* Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids
Inclusion Criteria
Inclusion Criteria:
* Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
* Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
* Patients must have:
* Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)
* Post-operative cranial MRI with and without gadolinium within 72 hours of surgery
* Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery
* Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent)
* Hemoglobin \>= 10.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* 1 month to \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status, coma or assisted ventilation prior to study enrollment
* Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible
* Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
* Patients must have:
* Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast)
* Post-operative cranial MRI with and without gadolinium within 72 hours of surgery
* Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery
* Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent)
* Hemoglobin \>= 10.0 g/dL (may receive red blood cell \[RBC\] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* 1 month to \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status, coma or assisted ventilation prior to study enrollment
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
47 Months
NCT Id
NCT02017964
Org Class
Network
Org Full Name
Children's Oncology Group
Org Study Id
ACNS1221
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II Study for the Treatment of Non-metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age
Primary Outcomes
Outcome Description
Progression-free survival (PFS) is defined as the time interval from diagnosis to the earliest of disease progression/recurrence or death from any cause, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.
Outcome Measure
Progression-free Survival (PFS)
Outcome Time Frame
2 years from diagnosis
Outcome Description
Overall Survival (OS) is defined as the time from diagnosis to death from any cause, or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's, as the data are not mature to 72 months.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Assessed up to 72 months, reported at 2 years from diagnosis
Outcome Description
Event-free survival (EFS) is defined as the time from diagnosis to the earliest of disease progression/recurrence, second malignancy or death from any cause, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's.
Outcome Measure
Event-free Survival (EFS)
Outcome Time Frame
2 years from diagnosis
Outcome Description
The percentage of patients with complete response (CR) at the end of induction (\~189 days) was reported and presented with the associated exact 95% confidence interval.
Outcome Measure
Percentage of Patients With Responses at 189 Days
Outcome Time Frame
189 days from start of treatment
Outcome Description
The percentage of patients with complete response (CR) at the end of therapy (\~273 days) was reported and presented with the associated exact 95% confidence interval.
Outcome Measure
Percentage of Patients With Responses at 273 Days
Outcome Time Frame
273 days from start of treatment
Secondary Ids
Secondary Id
NCI-2013-02379
Secondary Id
COG-ACNS1221
Secondary Id
ACNS1221
Secondary Id
s15-00476
Secondary Id
ACNS1221
Secondary Id
ACNS1221
Secondary Id
U10CA180886
Secondary Id
U10CA098543
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
3
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jonathan Gill
Investigator Email
jgill@montefiore.org
Investigator Phone
718-741-2331
Categories Mesh Debug
Skin Cancer --- NEUROECTODERMAL TUMORS
Cancer --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Cancer --- CARCINOMA
Orthopedics, Muscle & Bone --- BONE DISEASES
Arthritis --- MUSCULOSKELETAL DISEASES
Child Development & Autism --- MUSCULOSKELETAL DISEASES
Orthopedics, Muscle & Bone --- MUSCULOSKELETAL DISEASES
Digestive System --- STOMATOGNATHIC DISEASES
Blood & Bone Marrow Cancers --- CONGENITAL ABNORMALITIES
MeSH Terms
MEDULLOBLASTOMA
BASAL CELL NEVUS SYNDROME
GLIOMA
NEOPLASMS, NEUROEPITHELIAL
NEUROECTODERMAL TUMORS
NEOPLASMS, GERM CELL AND EMBRYONAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
NEUROECTODERMAL TUMORS, PRIMITIVE
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS, NERVE TISSUE
ODONTOGENIC CYSTS
JAW CYSTS
BONE CYSTS
CYSTS
CARCINOMA, BASAL CELL
CARCINOMA
NEOPLASMS, BASAL CELL
NEOPLASTIC SYNDROMES, HEREDITARY
BONE DISEASES, DEVELOPMENTAL
BONE DISEASES
MUSCULOSKELETAL DISEASES
JAW DISEASES
STOMATOGNATHIC DISEASES
ABNORMALITIES, MULTIPLE
CONGENITAL ABNORMALITIES
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
GENETIC DISEASES, INBORN
CARBOPLATIN
MENTAL STATUS AND DEMENTIA TESTS
CYCLOPHOSPHAMIDE
ETOPOSIDE
METHOTREXATE
MERPHOS
VINCRISTINE
COORDINATION COMPLEXES
ORGANIC CHEMICALS
NEUROPSYCHOLOGICAL TESTS
PSYCHOLOGICAL TESTS
BEHAVIORAL DISCIPLINES AND ACTIVITIES
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS
PODOPHYLLOTOXIN
TETRAHYDRONAPHTHALENES
NAPHTHALENES
POLYCYCLIC AROMATIC HYDROCARBONS
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
POLYCYCLIC COMPOUNDS
GLUCOSIDES
GLYCOSIDES
CARBOHYDRATES
AMINOPTERIN
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
VINCA ALKALOIDS
SECOLOGANIN TRYPTAMINE ALKALOIDS
INDOLE ALKALOIDS
ALKALOIDS
INDOLES
INDOLIZIDINES
INDOLIZINES