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

NCT01975116 | Completed Phase 1 DMC

• 3 other identifiers: PBTC-041NCI-2013-01710U01CA081457
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 11

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.

Conditions

Teratoid Tumor, Atypical; Choroid Plexus Neoplasms; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Brainstem Tumors; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumor, Primitive

Outcome Measures

Primary Outcomes (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

  Up to 6 weeks

Secondary Outcomes (3)

• Percentage of patients whose tumors are p53 positive (greater than or equal to 10% of tumor cells staining for p53)

  Up to 30 days post-treatment

• Type and frequency of p53 mutations present in the tumor specimens analyzed

  Up to 30 days post-treatment

• Change in tumor size

  Baseline to up to 30 days post-treatment

Study Arms (1)

Treatment: p28

EXPERIMENTAL

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

Interventions

azurin-derived cell-penetrating peptide p28 DRUG

Given IV

Also known as: azurin-derived CPP p28

Treatment: p28

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60614, United States

Location

National Cancer Institute Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Teratoid Tumor, Atypical; Choroid Plexus Neoplasms; Astrocytoma; Oligodendroglioma; Brain Stem Neoplasms; Glioblastoma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumors, Primitive

Interventions

azurin (50-77)

Condition Hierarchy (Ancestors)

Cerebral Ventricle Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Infratentorial Neoplasms

Study Officials

• Stewart Goldman

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 4, 2013
• Study Start: August 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: August 7, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (11)