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

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ClinicalTrials.gov Identifier: NCT01975116
Recruitment Status : Completed
First Posted : November 4, 2013
Last Update Posted : August 7, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium

Tracking Information
First Submitted Date  ICMJE October 28, 2013
First Posted Date  ICMJE November 4, 2013
Last Update Posted Date August 7, 2017
Study Start Date  ICMJE August 2013
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2013)
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 Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01975116 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2013)
  • 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 Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Teratoid Tumor, Atypical
  • Choroid Plexus Neoplasms
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Brainstem Tumors
  • Giant Cell Glioblastoma
  • Glioblastoma
  • Gliosarcoma
  • Medulloblastoma
  • Neuroectodermal Tumor, Primitive
Intervention  ICMJE Drug: azurin-derived cell-penetrating peptide p28
Given IV
Other Name: azurin-derived CPP p28
Study Arms  ICMJE 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.
Intervention: Drug: azurin-derived cell-penetrating peptide p28
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 27, 2014)
18
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2013)
40
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01975116
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: As determined in the Clinical Trial Agreement
Responsible Party Pediatric Brain Tumor Consortium
Study Sponsor  ICMJE Pediatric Brain Tumor Consortium
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Stewart Goldman Pediatric Brain Tumor Consortium
PRS Account Pediatric Brain Tumor Consortium
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP