This phase I trial studies the side effects and best dose of azurin-derived cell-penetrating peptide p28 (p28) in treating patients with recurrent or progressive central nervous system tumors. Drugs used in chemotherapy, such as azurin-derived cell-penetrating peptide p28, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Given IV
Children's Hospital Los Angeles
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
National Cancer Institute Pediatric Oncology Branch
Bethesda, Maryland, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
...and 1 more locations
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)
Will be estimated with its exact 95% confidence interval (CI).
Time frame: Up to 30 days post-treatment
Type and frequency of p53 mutations present in the tumor specimens analyzed
Will be summarized.
Time frame: Up to 30 days post-treatment
Change in tumor size
The proportion (and 95% CI) of subjects with an on-treatment tumor response or with clinical benefit will be provided.
Time frame: Baseline to up to 30 days post-treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.