Medulloblastoma Clinical Trial
Official title:
A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-Ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
Background:
- An experimental drug called ABT-888 has been studied in combination with temozolomide (a
type of chemotherapy) in adults who have certain kinds of cancer. ABT-88 has been shown to
increase tumor sensitivity to temozolomide and improve treatment outcomes in people who have
cancer. More research is needed to determine if this combination of drugs will work well as
an effective treatment for children who have brain tumors. This will be the first time this
combination has been studied in pediatric patients.
Objectives:
- To determine the maximum doses of ABT-888 and temozolomide when given in combination in
children with brain tumors.
- To learn how children metabolize and clear ABT-888 from their bodies so that appropriate
doses of this medication can be recommended for future clinical trials of this drug.
- To learn what side effects may occur when ABT-888 and temozolomide are given together.
- To learn how certain tumors respond to this combination of drugs by studying the
characteristics of these tumors in a laboratory.
Eligibility:
- Individuals less than 21 years of age who have been diagnosed with a cancer of the nervous
system (including brain and brain stem tumors) that has not responded to standard therapy.
Design:
- Before beginning the study, participants will have a full medical history and physical
examination, and may also be required to have scans of the brain and spine or provide
samples of cerebrospinal fluid.
- Treatment will consist of up to 13 28-day cycles of therapy, for a total of 52 weeks (1
year). Participants will receive a dose of ABT-888 twice daily for 5 days, and will
receive a dose of temozolomide once daily for 5 days, every 28 days. The morning dose of
ABT-888 will be given 60-90 minutes before the dose of temozolomide.
- Participants will have routine blood tests at least once a week throughout the treatment
cycles, and will have scans of the brain and spine performed as required by the
researchers.
Background
- A subset of patients with pediatric CNS tumors continue to have a poor prognosis despite
advances in surgery and radiation. Novel strategies are required for improving outcome
for these patients.
- Temozolomide, an oral alkylating agent, has shown modest activity in recurrent pediatric
CNS tumors, including high-grade gliomas, medulloblastoma/PNET, and low-grade gliomas.
- Temozolomide induces single-stranded DNA breaks, the majority of which are repaired by
the base excision repair (BER) pathway. Poly(ADP-ribose) polymerase, or PARP, is a
critical nuclear enzyme that binds to DNA breaks, recruits and activates key proteins in
the BER and other DNA repair pathways, halts DNA replication, and facilitates repair of
damaged DNA.
- ABT-888 is a potent and orally bioavailable PARP inhibitor that has been shown to
enhance cytotoxicity of temozolomide and other chemotherapy agents in several
pre-clinical models of human tumors.
Objectives
- To estimate the maximum tolerated dose (MTD) of ABT-888 in combination with temozolomide
in children with recurrent or refractory CNS tumors.
- To study the plasma pharmacokinetics (PK) of ABT-888 and PARP inhibition in peripheral
blood mononuclear cells (PBMC) in order to recommend a Phase 2 dose of ABT-888 in
combination with temozolomide in children with recurrent or refractory CNS tumors.
- To describe the toxicities of the combination of ABT-888 and temozolomide in children
with recurrent or refractory CNS tumors.
Eligibility
- Patient must be less than or equal to 21 years of age at registration.
- Patients with a diagnosis of a primary CNS malignancy (including low-grade glioma) that
is recurrent or refractory to standard therapy and for which there is no known curative
therapy Progression and recurrence will be documented by review of MRI scans. If time
permits we will have the diagnosis confirmed by the NCI Laboratory of Pathology.
Patients with intrinsic brain stem tumors must have radiographic evidence of
progression.
- Karnofsky Performance Scale (KPS for greater than 16 yrs of age) or Lansky Performance
Score (LPS for less than or equal to 16 years of age) greater than or equal to 50
assessed within two weeks of study enrollment.
- Patients must have recovered from the toxic effects of all prior therapy.
- Patients who are receiving dexamethasone must be on a stable or decreasing dose for at
least 1 week prior to registration.
Design
-ABT-888 will be given twice daily on day 1-5, and temozolomide will be given once daily on
day 1-5, every 28 days. The morning dose of ABT-888 will be given 60-90 minutes prior to
temozolomide.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT01326104 -
Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
|
Phase 2 | |
| Recruiting |
NCT04081701 -
68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
|
Phase 4 | |
| Completed |
NCT03273712 -
Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)
|
Phase 2 | |
| Active, not recruiting |
NCT02875314 -
HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
|
Phase 4 | |
| Completed |
NCT02441062 -
Impact of Ga-68 DOTATOC PET-CT Imaging in Management of Neuroendocrine Tumors
|
Phase 2 | |
| Completed |
NCT01171469 -
Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
|
Phase 1 | |
| Completed |
NCT00520936 -
A Study of Pemetrexed in Children With Recurrent Cancer
|
Phase 2 | |
| Completed |
NCT03257631 -
A Study of Pomalidomide Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors
|
Phase 2 | |
| Recruiting |
NCT04541082 -
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
|
Phase 1 | |
| Recruiting |
NCT04337177 -
Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors
|
Phase 1 | |
| Completed |
NCT02502708 -
Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors
|
Phase 1 | |
| Completed |
NCT01208831 -
An East Asian Study of LDE225
|
Phase 1 | |
| Completed |
NCT01505569 -
Auto Transplant for High Risk or Relapsed Solid or CNS Tumors
|
N/A | |
| Recruiting |
NCT04049669 -
Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
|
Phase 2 | |
| Recruiting |
NCT05125666 -
Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
|
Phase 2 | |
| Completed |
NCT03043391 -
Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children
|
Phase 1 | |
| Recruiting |
NCT05278208 -
Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT02724579 -
Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma
|
Phase 2 | |
| Recruiting |
NCT04402073 -
Personalized Risk-Adapted Therapy in Post-Pubertal Patients With Newly-Diagnosed Medulloblastoma
|
Phase 2 | |
| Completed |
NCT01708174 -
A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
|
Phase 2 |