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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Pediatric Brain Tumor Consortium
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT01975116
First received: October 28, 2013
Last updated: NA
Last verified: October 2013
History: No changes posted
  Purpose

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 Intervention Phase
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
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 40
Study Start Date: August 2013
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given IV
Other Name: azurin-derived CPP p28
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01975116

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Girish Dhall    323-361-4629    gdhall@chla.usc.edu   
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    pfisher@stanford.edu   
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    rpacker@cnmc.org   
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    sgoldman@luriechildrens.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    warrenk@mail.nih.gov   
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    dunkeli@mskcc.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    gurur002@mc.duke.edu   
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    maryam.fouladi@cchmc.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    pollaci@chp.edu   
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    alberto.broniscer@stjude.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    mxchinta@txch.org   
Principal Investigator: Murali M. Chintagumpala         
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Principal Investigator: Stewart Goldman Pediatric Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT01975116     History of Changes
Other Study ID Numbers: PBTC-041, NCI-2013-01710, PBTC-041, PBTC-041, U01CA081457
Study First Received: October 28, 2013
Last Updated: October 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Gliosarcoma
Oligodendroglioma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Choroid Plexus Neoplasms
Rhabdoid Tumor
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Cerebral Ventricle Neoplasms
Brain Neoplasms
Brain Diseases
Central Nervous System Diseases
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on September 18, 2014