p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors
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.
Childhood Atypical Teratoid/Rhabdoid Tumor
Childhood Choroid Plexus Tumor
Recurrent Childhood Anaplastic Astrocytoma
Recurrent Childhood Anaplastic Oligodendroglioma
Recurrent Childhood Brain Stem Glioma
Recurrent Childhood Giant Cell Glioblastoma
Recurrent Childhood Glioblastoma
Recurrent Childhood Gliosarcoma
Recurrent Childhood Medulloblastoma
Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
Drug: azurin-derived cell-penetrating peptide p28
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Will be summarized.
- Change in tumor size [ Time Frame: Baseline to up to 30 days post-treatment ] [ Designated as safety issue: No ]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|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (azurin-derived cell-penetrating peptide p28)
Patients receive azurin-derived cell-penetrating peptide p28 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.
Drug: azurin-derived cell-penetrating peptide p28
Other Name: azurin-derived CPP p28Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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||Recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Girish Dhall 323-361-4629 email@example.com|
|Principal Investigator: Girish Dhall|
|Lucile Packard Children's Hospital Stanford University||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Paul G. Fisher 650-721-5889 firstname.lastname@example.org|
|Principal Investigator: Paul G. Fisher|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Roger J. Packer 202-884-2120 email@example.com|
|Principal Investigator: Roger J. Packer|
|United States, Illinois|
|Lurie Children's Hospital-Chicago||Recruiting|
|Chicago, Illinois, United States, 60614|
|Contact: Stewart Goldman 312-227-4874 firstname.lastname@example.org|
|Principal Investigator: Stewart Goldman|
|United States, Maryland|
|National Cancer Institute Pediatric Oncology Branch||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Katherine E. Warren 301-435-4683 email@example.com|
|Principal Investigator: Katherine E. Warren|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Ira J. Dunkel 212-639-2153 firstname.lastname@example.org|
|Principal Investigator: Ira J. Dunkel|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Sridharan Gururangan 919-684-3506 email@example.com|
|Principal Investigator: Sridharan Gururangan|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Maryam Fouladi 513-803-0721 firstname.lastname@example.org|
|Principal Investigator: Maryam Fouladi|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15224|
|Contact: Ian F. Pollack 412-692-5881 email@example.com|
|Principal Investigator: Ian F. Pollack|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Alberto Broniscer 901-595-4925 firstname.lastname@example.org|
|Principal Investigator: Alberto Broniscer|
|United States, Texas|
|Baylor College of Medicine||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Murali M. Chintagumpala 832-822-4266 email@example.com|
|Principal Investigator: Murali M. Chintagumpala|
|Principal Investigator:||Stewart Goldman||Pediatric Brain Tumor Consortium|