ACNS1721: A Study of the Drug Veliparib with Radiation Therapy in Patients with Newly Diagnosed High-Grade Glioma

A Phase II Study of Veliparib (ABT-888, IND# 139199) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients with Newly Diagnosed High-Grade Glioma (HGG) without H3 K27M or BRAFV600E Mutations

Categories:

Brain Tumor

Solid Tumor

Phase I/II

Diseases Treated:

High-grade glioma

Eligibility Overview:

  • 3 to 25 years old
  • Newly diagnosed high-grade-glioma[SJ1] , such as anaplastic astrocytoma or glioblastoma
  • Negative test for H3 K27M mutation
  • Negative test for BRAFV600 mutation
  1. Brief Summary

    This study will select a subset of pediatric high-grade glioma based on molecular features at study entry that may be most likely to benefit from an experimental regimen that includes the Poly (ADP-ribose) polymerase (PARP) inhibitor, veliparib, during radiation therapy. This will be followed by veliparib in combination with temozolomide. Veliparib has a biological rationale for use in pediatric HGG and synergistic mechanisms of action in combination with either radiation therapy or temozolomide.

    This study will test whether the proposed combination therapy will improve event-free survival in patients with newly diagnosed HGG who are wild type for H3 K27M, IDH and BRAF (Stratum 1). The study will also include patients with IDH mutant glioma on Stratum 2. Outcome for all patients will be compared to clinically and molecularly matched historical control cohorts.

    Primary Objective

    • To determine whether veliparib (ABT-888), when added to radiotherapy and temozolomide, is effective for treatment of patients with newly diagnosed HGG whose tumors’ molecular profile are wild-type for H3 K27M, BRAFV600E and IDHI1/2.
    • To determine whether veliparib, when added to radiotherapy and temozolomide, is effective for treatment of patients with newly diagnosed HGG whose tumors’ molecular profile are wild-type for H3 K27M and BRAFV600E and harbor an IDHI1/2 mutation.

    Eligibility Criteria

    Inclusion criteria include:

    • Stratum 1 (IDH wild-type): 3 to 21 years old
    • Stratum 2 (IDH mutant): 3 to 25 years old
    • Eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1:
    • Newly diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma
      • Negative results for H3 K27M by immunohistochemistry
      • Negative results for BRAFV600 mutation by next-generation sequencing
    • Must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive diagnostic surgery

    Exclusion Criteria include:

    • Diffuse astrocytoma (grade 2)
    • Oligodendrogliomas (any grade)
    • Pleomorphic xanthoastrocytoma (PXA, any grade)
    • Primary tumor location of brainstem or spinal cord
    • Prior allogenic bone marrow transplant or double umbilical cord blood transplantation
    • Prior tumor-directed therapy, including radiation therapy, chemotherapy, molecularly targeted agents or immunotherapy for treatment of HGG other than surgery and/or corticosteroids

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee
    Collaborating sites in and outside the U.S.

  2. About this study

    A glioma is a type of cancer that grows as a tumor in the brain. A glioma is consideredhigh grade” when it is growing and spreading quickly.

    High-grade gliomas (HGGs) are hard to treat successfully. Standard treatment includes surgery to remove as much tumor as possible followed by radiation therapy (treatment with high-energy X-rays or high-energy protons) to kill cancer cells or keep them from growing. Other commonly used treatments may include chemotherapy (anti-cancer drugs) given during and after radiation treatment. Temozolomide is one of the chemotherapy drugs that may be used during and after radiation therapy to treat newly-diagnosed HGG. Maintenance therapy is therapy given after radiation therapy.

    In this study, doctors want to find treatments that will be better at getting rid of or shrinking HGGs and stopping them from coming back. One thing they want to do is try using different chemotherapy drugs during radiation therapy.

    If you are eligible for this study, you will receive a drug called veliparib. Veliparib is a drug that works differently than regular chemotherapy drugs. It kills cancer cells by blocking a protein that repairs DNA or genetic damage in cancer cells. In this study, veliparib will be given with radiation therapy and with temozolomide. This combination is considered experimental.

    You may or may not benefit from the treatment you receive in this study. However, the information learned from the study may benefit other patients in the future.

    Purpose of this clinical trial

    The main goal of this study is to find out if veliparib given with radiation therapy, followed by veliparib with temozolomide, works better than treatments that have been tried in the past. Researchers also want to find out what good and bad effects this treatment has on patients with newly diagnosed high-grade glioma.

    Eligibility overview

    • 3 to 25 years old
    • Newly diagnosed high-grade glioma, such as anaplastic astrocytoma or glioblastoma
    • Negative test for H3 K27M mutation
    • Negative test for BRAFV600 mutation
  3. ACNS1721  Quick View
    Sponsor
     
    Children’s Oncology Group 
    ClinicalTrials.gov identifier NCT03581292
    Trial start date October 2018
    Estimated enrollment 115 (across all sites)                                                                          
    Study type Interventional
    Study phase Phase II
    Conditions

    High-grade gliomas

    Ages 3 to 25 years old
    Principal investigator Santhosh Upadhyaya, MD (at St. Jude)
    Study site St. Jude Children’s Research Hospital  and collaborating sites in and outside the U.S.
    For a consultation or to discuss ACNS1721 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.