Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors
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|ClinicalTrials.gov Identifier: NCT02255461|
Recruitment Status : Recruiting
First Posted : October 2, 2014
Last Update Posted : September 28, 2017
|Condition or disease||Intervention/treatment||Phase|
|Childhood Choroid Plexus Tumor Childhood Ependymoblastoma Childhood Grade III Meningioma Childhood High-grade Cerebellar Astrocytoma Childhood High-grade Cerebral Astrocytoma Childhood Medulloepithelioma Recurrent Childhood Anaplastic Astrocytoma Recurrent Childhood Anaplastic Oligoastrocytoma Recurrent Childhood Anaplastic Oligodendroglioma Recurrent Childhood Brain Stem Glioma Recurrent Childhood Cerebellar Astrocytoma Recurrent Childhood Cerebral Astrocytoma Recurrent Childhood Giant Cell Glioblastoma Recurrent Childhood Glioblastoma Recurrent Childhood Gliomatosis Cerebri Recurrent Childhood Gliosarcoma Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor||Drug: palbociclib isethionate Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
I. To determine the maximum tolerated dose (MTD)/phase II recommended dose and describe toxicities related to PD-0332991 (palbociclib isethionate) in children with retinoblastoma protein 1 (Rb1) positive recurrent, progressive or refractory primary central nervous system (CNS) tumors.
II. To determine plasma pharmacokinetics of PD-0332991 in children with Rb1positive recurrent, progressive or refractory primary CNS tumors.
I. To record preliminary evidence of efficacy of PD-0332991 in children with recurrent CNS tumors.
II. To evaluate cyclin-dependent kinase (CDK)4/6, cyclin D1-3, cyclin-dependent kinase inhibitor 2A (Ink4a-ARF) copy-number variations in available tumor tissue by array comparative, genomic hybridization (aCGH).
III. To explore the potential relationships between the pharmacokinetics of PD-0332991 and pharmacodynamic response (e.g. percentage change in absolute neutrophil count [ANC], platelet counts).
IV. To explore the pharmacogenetic polymorphisms in PD-0332991 metabolizing enzymes and transporters and relate these polymorphisms to PD-0332991 pharmacokinetics.
OUTLINE: This is a dose-escalation study.
Patients receive palbociclib isethionate orally (PO) once daily (QD) on days 1-21. Treatment repeats every 4 weeks for 26 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of CDK 4-6 Inhibitor PD-0332991 (Palbociclib; IBRANCE) in Children With Recurrent, Progressive or Refractory Central Nervous System Tumors|
|Study Start Date :||October 2014|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||December 31, 2018|
Experimental: Treatment (palbociclib isethionate)
Patients receive palbociclib isethionate PO QD on days 1-21. Treatment repeats every 4 weeks for 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: palbociclib isethionate
Other Name: 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one, 827022-33-3, palbociclib, PD 0332991-0054, PD-0332991, PD-332991, PF-00080665-73
Other: pharmacological study
Other Name: pharmacological studies
Other: laboratory biomarker analysis
- MTD of palbociclib isethionate defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose limiting toxicity and the next higher dose level has been determined to be too toxic [ Time Frame: 4 weeks ]Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.
- Incidence of adverse events [ Time Frame: Up to 30 days ]Adverse event data will be summarized in tables which will incorporate dose, attribution as well as grade information.
- Objective responses (partial response + complete response) [ Time Frame: Up to 30 days ]Will be described by dose and by histology. Prolonged disease stabilizations will be reported in a descriptive fashion.
- Individual pharmacokinetic parameters of interest, such as apparent volume of the central compartment (Vc/F), elimination rate constant (Ke), half-life (t1/2), apparent oral clearance (CL/F), and area under the plasma concentration time curve (AUC) [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 10, 24, 48 hours after dose (day 1, course 1) and pre-dose, 1, 2, 4, 8, 10, 24 hours after dose (day 21, course 1) ]Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form. Pharmacokinetic parameters of interest, such as Vc/F, Ke, t1/2, CL/F, and AUC will be estimated using compartmental methods. Dose proportionality in pharmacokinetic parameters will be investigated by performing one-way analysis of variance on dose-normalized parameters.
- Population pharmacokinetic parameters [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, 10, 24, 48 hours after dose (day 1, course 1) and pre-dose, 1, 2, 4, 8, 10, 24 hours after dose (day 21, course 1) ]Will be estimated using nonlinear mixed effects modeling methods. Once the population parameters and corresponding covariance matrix are estimated, individual estimates can be obtained using post hoc analysis.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02255461
|Contact: Wint M Swe, MBA, MBBSfirstname.lastname@example.org|
|Contact: Stacye Richardsonemail@example.com|
|United States, California|
|Childrens Hospital Los Angeles||Recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Girish Dhall 323-361-4629 firstname.lastname@example.org|
|Principal Investigator: Girish Dhall|
|Lucile Packard Children Hospital Stanford University||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Paul G. Fisher 650-721-5889 email@example.com|
|Principal Investigator: Paul G. Fisher|
|United States, District of Columbia|
|Childrens National Medical Center||Recruiting|
|Washington, D.C., District of Columbia, United States, 20010-2970|
|Contact: Eugene Hwang, MD 202-476-5046 firstname.lastname@example.org|
|Principal Investigator: Lindsay B Kilburn, MD|
|Sub-Investigator: Roger Packer, MD|
|Sub-Investigator: Brain Rood, MD|
|Sub-Investigator: Eugene Hwang, MD|
|United States, Illinois|
|Lurie Childrens Hospital-Chicago||Recruiting|
|Chicago, Illinois, United States, 60614|
|Contact: Stewart Goldman 312-227-4874 email@example.com|
|Principal Investigator: Stewart Goldman, MD|
|Sub-Investigator: Jason Fangusaro, MD|
|Sub-Investigator: Rishi Lulla, MD|
|Sub-Investigator: Natasha Pillay-Smiley, MD|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Ira Dunkel 212-639-2153 firstname.lastname@example.org|
|Principal Investigator: Ira Dunkel|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: David Van Mater, MD, PhD 919-684-3401 email@example.com|
|Principal Investigator: David Van Mater|
|United States, Ohio|
|Cincinnati Children Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Maryam Fouladi 513-803-0721 firstname.lastname@example.org|
|Principal Investigator: Maryam Fouladi|
|United States, Pennsylvania|
|Children Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15224|
|Contact: Ian Pollack 412-692-5881 Pollaci@chp.edu|
|Sub-Investigator: Ian Pollack, MD|
|Principal Investigator: A. Kim Ritchey, MD|
|United States, Tennessee|
|St. Jude Children Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Giles Robinson, MD 901-595-2907 email@example.com|
|Principal Investigator: Zsila Sadighi, MD|
|Sub-Investigator: Amar Gajjar, MD|
|United States, Texas|
|Texas Childrens Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Patricia M. Baxter, MD 832-824-4681 firstname.lastname@example.org|
|Sub-Investigator: Murali M. Chintagumpala|
|Principal Investigator: Patricia Baxter|
|United States, Washington|
|Seattle Children Hospital||Recruiting|
|Seattle, Washington, United States, 98105|
|Contact: Sarah Leary 206-987-2106 email@example.com|
|Principal Investigator: Sarah Leary|
|Principal Investigator:||David Van Mater, MD||Pediatric Brain Tumor Consortium|