Teratoid Tumor, AtypicalPhase 1NCT01975116
p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors
A Phase 1 study testing azurin-derived cell-penetrating peptide p28 in people with Teratoid Tumor, Atypical and Choroid Plexus Neoplasms, run by Pediatric Brain Tumor Consortium at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Teratoid Tumor, Atypical, Choroid Plexus Neoplasms, Anaplastic Astrocytoma
- What is being tested?
- azurin-derived cell-penetrating peptide p28
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 11 sitesUnited States
- Study dates
- Aug 2013to Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Show all 25Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
National Cancer Institute Pediatric Oncology Branch
Bethesda, Maryland, 20892
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University Medical Center
Durham, North Carolina, 27710
Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Teratoid Tumor, Atypical, Choroid Plexus Neoplasms, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Brainstem Tumors, Giant Cell Glioblastoma
- Being tested
- azurin-derived cell-penetrating peptide p28
- Medical subject headings
- Teratoid Tumor, Atypical, Choroid Plexus Neoplasms, Astrocytoma, Oligodendroglioma, Brain Stem Neoplasms, Glioblastoma, Gliosarcoma, Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azurin-derived cell-penetrating peptide p28Drug
Also called azurin-derived CPP p28
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: azurin-derived cell-penetrating peptide p28 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Will be estimated with its exact 95% confidence interval (CI).
Measured: Up to 30 days post-treatment
Type and frequency of p53 mutations present in the tumor specimens analyzed
Will be summarized.
Measured: Up to 30 days post-treatment
Change in tumor size
The proportion (and 95% CI) of subjects with an on-treatment tumor response or with clinical benefit will be provided.
Measured: Baseline to up to 30 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2013 (estimated)
- Study startAug 2013
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Teratoid Tumor, AtypicalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Brain Tumor Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Stewart Goldman, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01975116
- Sponsor's protocol ID
- PBTC-041
- Other IDs
- NCI-2013-01710, PBTC-041, PBTC-041, U01CA081457
- Status last verified
- Aug 2017
- First submitted
- 28 Oct 2013
- Last updated
- 7 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: As determined in the Clinical Trial Agreement
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01975116
- Acronym / sponsor ID
- PBTC-041
- Conditions
- Teratoid Tumor, Atypical, Choroid Plexus Neoplasms, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Brainstem Tumors, Giant Cell Glioblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Pediatric Brain Tumor ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 4 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment: p28 | Experimental | Drug: azurin-derived cell-penetrating peptide p28Pts 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. |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| azurin-derived cell-penetrating peptide p28Also: azurin-derived CPP p28Given IV | Drug | Treatment: p28 |
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
3 secondary outcomes
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
Type and frequency of p53 mutations present in the tumor specimens analyzed
Time frame: Up to 30 days post-treatment
Change in tumor size
Time frame: Baseline to up to 30 days post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2017.
- Individual participant dataSharing planned: Yes. As determined in the Clinical Trial Agreement
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stewart Goldman principal investigator
Pediatric Brain Tumor Consortium
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing azurin-derived cell-penetrating peptide p28 in people with Teratoid Tumor, Atypical and Choroid Plexus Neoplasms, run by Pediatric Brain Tumor Consortium at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2017.