Clinical Trial: Pomalidomide in Treating Younger Patients With Recurrent, Progressive or Refractory Central Nervous System Tumors
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: A Phase I Trial of Pomalidomide for Children With Recurrent, Progressive or Refractory CNS Tumors
Brief Summary: This phase I trial studies the side effects and best dose of pomalidomide in treating younger patients with tumors of the brain or spine (central nervous system) that have come back or are continuing to grow. Pomalidomide may interfere with the ability of tumor cells to grow and spread and may also stimulate the immune system to kill tumor cells.
Detailed Summary:
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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 interleukin [IL]-12, IL-2, IL-15, granulocyte-macrophage colony-stimulating factor [GM-CSF]).
OUTLINE: This is a dose-escalation study.
Patients rec
Sponsor: National Cancer Institute (NCI)
Current Primary Outcome:
- MTD/RP2D of pomalidomide, defined as the highest dose level at which 6 patients have been treated with at most 1 experiencing dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic (>= 2 DLT) [ Time Frame: Up to 28 days ]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.
- PK 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 PK 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 PK of pomalidomide will be evaluated. Descriptive statistics provided as appropriate. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form.
Original Primary Outcome:
- MTD/RP2D of pomalidomide, defined as the highest dose level at which 6 patients have been treated with at most 1 experiencing dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic (>= 2 DLT) [ Time Frame: 28 days ]Defined separately for Arm A and Arm B.
- Pharmacokinetic (PK) 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 PK 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 PK of pomalidomide will be evaluated. Descriptive statistics provided as appropriate. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form.
Current Secondary Outcome:
- Duration of response [ Time Frame: The time from the initial documented response (CR, PR or long-term SD) to the first confirmed PD, 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 (EFS) [ Time Frame: The time from study enrollment until the time of PD, 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 EFS 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.
- Response rate (complete response [CR], partial response [PR], and stable disease [SD]) [ 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., CR, PR, SD and progressive disease [PD]). Descriptive summaries of response per dose level within each stratum may also be provided.
Original Secondary Outcome: Same as current
Information By: National Cancer Institute (NCI)
Dates:
Date Received: April 13, 2015
Date Started: July 2015
Date Completion:
Last Updated: April 19, 2017
Last Verified: April 2017
