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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01975116
Recruitment Status : Completed
First Posted : November 3, 2013
Last Update Posted : August 7, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium

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.

Condition or disease Intervention/treatment Phase
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

Detailed Description:


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : August 2013
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Arm Intervention/treatment
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
Given IV
Other Name: azurin-derived CPP p28

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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).

  2. Type and frequency of p53 mutations present in the tumor specimens analyzed [ Time Frame: Up to 30 days post-treatment ]
    Will be summarized.

  3. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have histologically confirmed primary progressive, recurrent or refractory CNS tumors with no known curative therapies limited to high grade glioma, such as glioblastoma multiforme, medulloblastoma, primitive neuroectodermal tumor, atypical teratoid/rhabdoid tumor, anaplastic astrocytoma, high-grade astrocytoma not otherwise specified (NOS), anaplastic oligodendroglioma, or choroid plexus carcinoma; or diffuse intrinsic pontine glioma; the requirements for histological verification are waived for diffuse intrinsic pontine glioma
  • Patients must not have received myelosuppressive chemotherapy or immunotherapy within 3 weeks of registration (6 weeks if prior nitrosourea)
  • Patients must have received their last dose of biologic agent >= 7 days prior to study registration
  • Steroid dose should be stable or decreasing for at least 1 week prior to registration
  • If prior therapy was monoclonal antibody, 30 days or 3 half-lives must have elapsed (whichever is longer), prior to registration
  • Patient must be off all colony stimulating factors > 1 week prior to registration (filgrastim [GCSF], sargramostim [GM CSF], erythropoietin)
  • Any craniospinal irradiation must have taken place >= 3 months prior to registration >= 8 weeks for local irradiation to primary tumor; >= 2 weeks prior to study entry for focal irradiation for symptomatic metastatic sites
  • Karnofsky performance scale (KPS) (for > 16 years [yrs] of age) or Lansky performance score (LPS) (for =< 16 years of age) >= 50 assessed within two weeks prior to registration
  • Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration
  • Absolute neutrophil count >= 1000/ mm^3 (unsupported)
  • Platelets >= 100,000/ mm^3 (unsupported)
  • Hemoglobin >= 8g/dL (with or without packed red blood cells [PRBC] transfusion)
  • Total bilirubin =< 1.5 times upper limit of normal for age
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 times institutional upper limit of normal for age
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3.0 times institutional upper limit of normal for age
  • Blood glucose within normal limits for age (If above institutional normal limits must be repeated as fasting and then within normal limits [WNL] for age)
  • Creatinine clearance or nuclear glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age as follows:

    • =< 5 years: 0.8 mg/dL
    • > 5 to =< 10 years: 1 mg/dL
    • > 10 to =< 15 years: 1.2 mg/dL
    • > 15 years: 1.5 mg/dL
  • Albumin >= 2 g/dL
  • Female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test
  • Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 6 months after the last drug administration
  • Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who are receiving any other investigational agents
  • Patients with known inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
  • Only tumor types listed above are allowed; low grade gliomas (with and without neurofibromin 1 [NF1]) and ependymomas are excluded
  • History of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to murine protein-containing products
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with p28

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01975116

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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, D.C., 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
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
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Principal Investigator: Stewart Goldman Pediatric Brain Tumor Consortium
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Responsible Party: Pediatric Brain Tumor Consortium Identifier: NCT01975116    
Other Study ID Numbers: PBTC-041
NCI-2013-01710 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PBTC-041 ( Other Identifier: Pediatric Brain Tumor Consortium )
PBTC-041 ( Other Identifier: CTEP )
U01CA081457 ( U.S. NIH Grant/Contract )
First Posted: November 3, 2013    Key Record Dates
Last Update Posted: August 7, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: As determined in the Clinical Trial Agreement
Additional relevant MeSH terms:
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Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Brain Stem Neoplasms
Choroid Plexus Neoplasms
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Infratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Ventricle Neoplasms