p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors
|Teratoid Tumor, Atypical Choroid Plexus Neoplasms Anaplastic Astrocytoma Anaplastic Oligodendroglioma Brainstem Tumors Giant Cell Glioblastoma Glioblastoma Gliosarcoma Medulloblastoma Neuroectodermal Tumor, Primitive||Drug: azurin-derived cell-penetrating peptide p28||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of p28 (NSC745104), a Non-HDM2 Mediated Peptide Inhibitor of p53 Ubiquitination in Pediatric Patients With Recurrent or Progressive CNS Tumors|
- Number of patients experiencing dose-limiting toxicities (DLT) defined as any adverse event or grade 3 or 4 toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 6 weeks ]
- Percentage of patients whose tumors are p53 positive (greater than or equal to 10% of tumor cells staining for p53) [ Time Frame: Up to 30 days post-treatment ]Will be estimated with its exact 95% confidence interval (CI).
- Type and frequency of p53 mutations present in the tumor specimens analyzed [ Time Frame: Up to 30 days post-treatment ]Will be summarized.
- Change in tumor size [ Time Frame: Baseline to up to 30 days post-treatment ]The proportion (and 95% CI) of subjects with an on-treatment tumor response or with clinical benefit will be provided.
|Study Start Date:||August 2013|
|Study Completion Date:||April 2015|
|Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment: p28
Pts receive azurin-derived cell-penetrating peptide p28 IV over 15 min 3x/week for 4 wks. Tx repeats every 6 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Drug: azurin-derived cell-penetrating peptide p28
Other Name: azurin-derived CPP p28
I. To establish whether the adult recommended phase II dose of 3x/week bolus infusions of p28is safe for pediatric patients with recurrent/refractory central nervous system (CNS) tumors.
II. To describe dose-limiting toxicities of 3x/week bolus infusions of p28 in pediatric patients with recurrent/refractory CNS tumors.
III. To evaluate and characterize the plasma pharmacokinetics of p28 in children with recurrent/ refractory CNS tumors.
I. To describe in the context of a phase I trial any observed antitumor activity of p28.
II. To investigate levels of p53 in clinical tumor specimens of patients with pediatric gliomas and other pediatric CNS tumors treated with p28.
III. To document the type/site(s) of p53 mutation in tumor tissue specimens. IV. To evaluate and characterize the intratumoral pharmacokinetics of p28 in children with recurrent/ refractory CNS tumors, if available.
OUTLINE: This is a dose-escalation study.
Patients receive azurin-derived cell-penetrating peptide p28 intravenously (IV) over 15 minutes thrice weekly for 4 weeks. Treatment repeats every 6 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for at least 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01975116
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|Lucile Packard Children's Hospital Stanford University|
|Palo Alto, California, United States, 94304|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Illinois|
|Lurie Children's Hospital-Chicago|
|Chicago, Illinois, United States, 60614|
|United States, Maryland|
|National Cancer Institute Pediatric Oncology Branch|
|Bethesda, Maryland, United States, 20892|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Stewart Goldman||Pediatric Brain Tumor Consortium|