Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 17-009225
    NCT ID: NCT02724579
    Sponsor Protocol Number: ACNS1422

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

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

Exclusion Criteria:

  • 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

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Carola A Arndt, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20403517

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