Clinical Trial: p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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.

Sponsor: Pediatric Brain Tumor Consortium

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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.

Original Secondary Outcome: Same as current

Information By: Pediatric Brain Tumor Consortium

Dates:
Date Received: October 28, 2013
Date Started: August 2013
Date Completion:
Last Updated: October 21, 2016
Last Verified: October 2016