Clinical trial · Interventional
Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas
A Phase I/II Study of ABT-888, An Oral Poly(ADP-ribose) Polymerase Inhibitor, and Concurrent Radiation Therapy, Followed by ABT-888 and Temozolomide, in Children With Newly Diagnosed Diffuse Pontine Gliomas (DIPG)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This phase I/II trial studies the side effects and the best dose of veliparib when given together with radiation therapy and temozolomide and to see how well they work in treating younger patients newly diagnosed with diffuse pontine gliomas. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing. Giving veliparib with radiation therapy and temozolomide may kill more tumor cells.
Conditions
Conditions (13)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Anaplastic Astrocytoma | Anaplastic Astrocytoma | CURATED_BROADER | 0.80 |
| Brain Stem Glioma | Brain Stem Glioma | ONTOLOGY_EXACT | 0.90 |
| Childhood Mixed Glioma | Childhood Mixed Glioma | ONTOLOGY_EXACT | 0.98 |
| Fibrillary Astrocytoma | Fibrillary Astrocytoma | ONTOLOGY_EXACT | 0.90 |
| Giant Cell Glioblastoma | Giant Cell Glioblastoma | ONTOLOGY_EXACT | 0.90 |
| Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
| Gliosarcoma | Gliosarcoma | ONTOLOGY_EXACT | 0.90 |
| Untreated Childhood Anaplastic Astrocytoma |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 3-Dimensional Conformal Radiation Therapy | Radiation | — | UNRESOLVED |
| Intensity-Modulated Radiation Therapy | Radiation | — | UNRESOLVED |
| Laboratory Biomarker Analysis | Other | — | UNRESOLVED |
| Pharmacological Study | Other | — | UNRESOLVED |
| Temozolomide | Drug | Temozolomide | ALIAS |
| Veliparib | Drug | Veliparib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment (veliparib, temozolomide, 3D-CRT, IMRT)
- description
- DOSE-ESCALATION: Patients receive veliparib PO BID 5 days a week for 6-7 weeks. Patients also undergo concurrent 3D-CRT or IMRT QD 5 days a week for 6-7 weeks. MAINTENANCE THERAPY: Beginning 3-4 weeks later, patients receive veliparib PO BID on days 1-5 and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
- interventionNames
- Radiation: 3-Dimensional Conformal Radiation Therapy
- Radiation: Intensity-Modulated Radiation Therapy
- Other: Laboratory Biomarker Analysis
- Other: Pharmacological Study
- Drug: Temozolomide
- Drug: Veliparib
Primary outcomes (4)
- measure
- Maximum-tolerated Dose of Veliparib Defined as Highest Dose Level With Fewer Than 2 Dose Limiting Toxicities in 6 Patients as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)
- timeFrame
- 10 weeks
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 21 Years
Show eligibility criteria text
Inclusion Criteria: * Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic mixed glioma, or fibrillary astrocytoma * Patients with juvenile pilocytic astrocytoma, pilomyxoid astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; * Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician * Patient must be able to swallow oral medications to be eligible for study enrollment * Karnofsky \>= 50% for patients \> 16 years of age or Lansky \>= 50% for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * Patients must have not received any prior therapy other than surgery and/or steroids * Absolute neutrophil count \>= 1,000/mm\^3 * Platelets \>= 100,000/mm\^3 (unsupported) * Hemoglobin \>= 10 g/dL (unsupported) * Total bilirubin =\< 1.5 times upper limit of normal (ULN) for age * Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 5 x institutional upper limit of normal for age * Albumin \>= 2 g/dL * 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: * 0.6 mg/dL (1 to \< 2 years of age) * 0.8 mg/dL (2 to \< 6 years of age) * 1.0 mg/dL (6 to \< 10 years of age) * 1.2 mg/dL (10 to \< 13 years of age) * 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to \< 16 years of age) * 1.7 mg/dL (male) or 1.4 mg/dL (female) (\>= 16 years of age) * Female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test * Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study * Signed informed consent according to institutional guidelines must be obtained; assent, when appropriate, will be obtained according to institutional guidelines Exclusion Criteria: * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results * Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy * Patients with active seizures or a history of seizure are not eligible for study entry, with the exception of patients with documented febrile seizure
References
Publications (2)
- DERIVEDSesen J, Driscoll J, Shah N, Moses-Gardner A, Luiselli G, Alexandrescu S, Zurakowski D, Baxter PA, Su JM, Pricola Fehnel K, Smith ER. Neogenin is highly expressed in diffuse intrinsic pontine glioma and influences tumor invasion. Brain Res. 2021 Jul 1;1762:147348. doi: 10.1016/j.brainres.2021.147348. Epub 2021 Feb 9. No abstract available. PMID 33571520
- DERIVEDBaxter PA, Su JM, Onar-Thomas A, Billups CA, Li XN, Poussaint TY, Smith ER, Thompson P, Adesina A, Ansell P, Giranda V, Paulino A, Kilburn L, Quaddoumi I, Broniscer A, Blaney SM, Dunkel IJ, Fouladi M. A phase I/II study of veliparib (ABT-888) with radiation and temozolomide in newly diagnosed diffuse pontine glioma: a Pediatric Brain Tumor Consortium study. Neuro Oncol. 2020 Jun 9;22(6):875-885. doi: 10.1093/neuonc/noaa016. PMID 32009149