Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma
A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients
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Clinical Trial Information
Trial Contact: Spinelli, Jennifer; Parker, Melanie; Armatti, Julie M; Doyle, Katherine M; Dubberly, Paige D
Trial Phone: 321.841.5357 ; 321-843-1036 ; 321-843-5284 ; 3218412008 ; 321-841-7561
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IRB No: ACNS1422
Protocol Abbrev: ACNS1422
Principal Investigator: Amy A. Smith, MD
Phase: Drug: Phase II
Age Group: Pediatric
Secondary Protocol No: ACNS1422
Treatment: Drug: Cisplatin, Drug: Cyclophosphamide, Other: Laboratory Biomarker Analysis, Drug: Lomustine, Radiation: Radiation Therapy, Drug: Vincristine Sulfate
Therapies Involved: Chemotherapy
ClinicalTrials.gov ID: NCT02724579
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Objective
To estimate the progression-free survival (PFS) of children >= 3 years of age with wingless-type MMTV integration site family (WNT)/WNT-driven average-risk medulloblastoma using reduced craniospinal radiotherapy (CSI) (18 Gray [Gy]) with a limited target volume boost to the tumor bed of 36 Gy for a total of 54 Gy and reduced chemotherapy approach (no vincristine [vincristine sulfate] during radiotherapy and reduced-dose maintenance chemotherapy) and to monitor the PFS for early evidence that the outcome is unacceptable
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Key Eligibility
Inclusion Criteria:
• Patients must be newly diagnosed and have a confirmed molecular diagnosis of classical histologic type (non large cell/anaplastic [LC/A]) WNT medulloblastoma from rapid central pathology screening review on APEC14B1 (immunohistochemistry [IHC]/molecular screening [positive nuclear beta (B)-catenin by IHC and positive for catenin beta 1 [CTNNB1] mutation) and confirmation of =< 1.5 cm^2 maximal cross-sectional area of residual tumor from rapid central imaging review
• Patient must have negative lumbar cerebrospinal fluid (CSF) cytology; 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 eligibility confirmed by rapid central imaging review on APEC14B1; standard whole brain magnetic resonance imaging (MRI) with and without contrast (gadolinium) and spine MRI with contrast (gadolinium) must be performed at the following time points:
◦Pre-operative to include an MRI of the brain with and without contrast (including post-contrast three-dimensional [3D] T1-weighted image [T1WI] and post-contrast fluid-attenuated inversion recovery [FLAIR])
◦Pre-operative spinal MRI with gadolinium; post-operative staging spinal MRI may be obtained if pre-operative imaging is not possible or is suboptimal; pre-operative spine imaging is strongly preferred, due to the potential of post-operative sequelae, which could affect metastasis detection
◦Post-operative brain MRI within 72 hours of surgery
• Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1422
◦Patients must be enrolled within 36 days of definitive diagnostic surgery (day 0)
◾Note: patients must begin treatment within 36 days of definitive surgery
• Patients must have no previous radiotherapy or chemotherapy other than corticosteroids
• 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:
◦3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and females)
◦6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)
◦10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)
◦13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL (females)
◦>= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
◾The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
• Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the upper limit of normal [ULN] for SGPT is 45 U/L)
• 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 epilepticus, a coma or on assisted ventilation at the time of study enrollment
• All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
