Summary

for people ages 3-21 (full criteria)
at Oakland, California and other locations
study started
estimated completion:

Description

Summary

This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, 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. Giving reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Official Title

A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

Details

PRIMARY OBJECTIVES:

  1. 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.

SECONDARY OBJECTIVES:

  1. To prospectively test the hypothesis that deoxyribonucleic acid (DNA) methylation profiling will result in ?real-time? classification of WNT-driven medulloblastoma.

II. To use the ALTE07C1 protocol to prospectively evaluate and longitudinally model the cognitive, social, emotional and behavioral functioning of children who are treated with reduced CSI (18 Gy) with a limited target volume boost to the tumor bed (to a total of 54 Gy) and reduced chemotherapy (reduced cisplatin, vincristine and lomustine [CCNU]).

TERTIARY OBJECTIVES:

  1. To explore whether DNA methylation profiling of medulloblastoma samples will result in a ?real-time? predictive classification scheme for the Sonic Hedgehog (SHH), Group 3 and Group 4 medulloblastoma subgroups according to the Heidelberg classifier.

OUTLINE:

RADIATION THERAPY: Beginning 4-5 weeks after surgery, patients undergo craniospinal radiation therapy 5 days a week for 6 weeks.

MAITENANCE THERAPY (WEEKS 1, 3, 5, and 7): Beginning 4-6 weeks after completion of radiation therapy patients receive lomustine orally (PO) on day 1, vincristine sulfate intravenously (IV) over 1 minute or via minibag on days 1, 8, and 15, and cisplatin IV over 6 hours on day 1. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY (WEEKS 2, 4, AND 6): Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 2, mesna IV over 15-30 minutes on days 1 and 2, and vincristine sulfate IV over 1 minute or via minibag on days 1 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually for 6 years.

Keywords

Medulloblastoma Untreated Childhood Medulloblastoma Cisplatin Cyclophosphamide Vincristine Lomustine Laboratory Biomarker Analysis Radiation Therapy Vincristine Sulfate

Eligibility

You can join if…

Open to people ages 3-21

  • 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 cm2 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 m2 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

You CAN'T join if...

  • Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
  • Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids
  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Locations

  • Children's Hospital and Research Center at Oakland accepting new patients
    Oakland California 94609-1809 United States
  • Children's Hospital Central California accepting new patients
    Madera California 93636-8762 United States
  • Lucile Packard Children's Hospital Stanford University accepting new patients
    Palo Alto California 94304 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Oncology Group
ID
NCT02724579
Phase
Phase 2
Study Type
Interventional
Last Updated
August 3, 2018