Pomalidomide in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02415153|
Recruitment Status : Active, not recruiting
First Posted : April 14, 2015
Last Update Posted : October 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Neurofibromatosis Type 1 Recurrent Central Nervous System Neoplasm Recurrent Childhood Brain Stem Glioma Recurrent Childhood Visual Pathway Glioma Refractory Central Nervous System Neoplasm||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Pomalidomide||Phase 1|
I. To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of pomalidomide, in children from >= 3 years to < 21 years of age with recurrent, progressive or refractory central nervous system (CNS) tumors when given once daily for 21 consecutive days of a 28-day course.
II. To describe the toxicity profile and dose-limiting toxicities of pomalidomide in children from >= 3 years to < 21 years of age with recurrent, progressive or refractory CNS tumors.
III. To characterize the pharmacokinetics of pomalidomide when administered orally in children from >= 3 years old to < 21 years of age with recurrent, progressive or refractory CNS tumors and study the association of pharmacokinetic (PK) parameters with age and steroid use.
I. To explore the preliminary efficacy of pomalidomide in this patient population as defined by radiographic response rate, duration of response, and event-free survival (EFS) within the confines of a Phase 1 study. *For the purposes of this study, long-term stable disease will be considered a response (defined as stable disease for >= 6 courses).
II. To investigate a relationship between pomalidomide dose and exposure with radiographic response and changes in immune function (for example, T-cell subsets, natural killer [NK] cell activity, granzyme B and circulating levels of IL-12, IL-2, IL-15, GM-CSF).
OUTLINE: This is a dose-escalation study.
Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Pomalidomide for Children With Recurrent, Progressive, or Refractory CNS Tumors|
|Actual Study Start Date :||July 14, 2015|
|Estimated Primary Completion Date :||March 31, 2020|
Experimental: Treatment (pomalidomide)
Patients receive pomalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Optional correlative studies
Other: Pharmacological Study
- Maximum tolerated dose/recommended phase II dose of pomalidomide [ Time Frame: Up to 28 days ]Will be defined as the highest dose level at which 6 patients have been treated with at most 1 experiencing dose-limiting toxicity and the next higher dose level has been determined to be too toxic (>= 2 dose-limiting toxicity). All safety data will be presented by dose cohort (intended dose) within each stratum separately. Adverse events will be tabulated by grade and attribution to the study agent.
- Pharmacokinetics parameters of pomalidomide [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 24 hours post-dose day 1 of course 1; 1 sample pre-dose any day between days 3-21 of course 1 ]Population estimates of pharmacokinetics parameters for pomalidomide will be estimated, and intra- and inter-subject variability of these parameters will be characterized. The effect of demographics/covariates (e.g., age, body weight, gender, prior treatment and use of concomitant medications, etc.) on the pharmacokinetics of pomalidomide will be evaluated. Descriptive statistics provided as appropriate. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form.
- Response rate (complete response, partial response, and stable disease) [ Time Frame: Up to 2 years ]The response rate will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided for the entire trial cohort as well as for each stratum separately and will be summarized by each response category (i.e., complete response, partial response, stable disease and progressive disease). Descriptive summaries of response per dose level within each stratum may also be provided.
- Duration of response [ Time Frame: The time from the initial documented response (complete response, partial response or long-term stable disease) to the first confirmed progressed disease, assessed up to 2 years ]Assessed using the Kaplan-Meier method to calculate the median time as well as the proportion remaining event free at given time points. The corresponding 95% confidence intervals will be presented. All results will be presented by stratum as well as combined.
- Event-free survival [ Time Frame: The time from study enrollment until the time of progressive disease, second-(ary) malignancy or death from any cause on study treatment, assessed up to 2 years ]Assessed using the Kaplan-Meier method to calculate the median event-free survival as well as the proportion remaining event free at given time points. The corresponding 95% confidence intervals will be presented. All results will be presented by stratum as well as for the entire cohort.
- Change in levels of biologic correlates [ Time Frame: Baseline to up to day 21 ]A general linear model (with appropriate transformations if needed) will be used to explore a dose-response relationship between levels of the biologic and immunologic correlates and pomalidomide dose. The longitudinal changes in these markers will be modeled using mixed effects models and explore associations with responses as well as with event free survival, within the constraints of a phase I trial in a descriptive fashion. In addition, associations between changes in circulating endothelial and precursor cells with angiogenic associated proteins will be explored via plots and correlation coefficients.
- Change in levels of immunologic correlates [ Time Frame: Baseline to up to day 21 ]A general linear model (with appropriate transformations if needed) will be used to explore a dose-response relationship between levels of the biologic and immunologic correlates and pomalidomide dose. The longitudinal changes in these markers will be modeled using mixed effects models and explore associations with responses as well as with event free survival, within the constraints of a Phase I trial in a descriptive fashion. In addition, associations between changes in circulating endothelial and precursor cells with angiogenic associated proteins will be explored via plots and correlation coefficients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02415153
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|Lucile Packard Children's Hospital Stanford University|
|Palo Alto, California, United States, 94304|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Illinois|
|Lurie Children's Hospital-Chicago|
|Chicago, Illinois, United States, 60611|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|National Cancer Institute|
|Rockville, Maryland, United States, 20850|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jason R Fangusaro||Pediatric Brain Tumor Consortium|