Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma
|ClinicalTrials.gov Identifier: NCT01553149|
Recruitment Status : Active, not recruiting
First Posted : March 14, 2012
Last Update Posted : October 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Neurofibromatosis Type 1 Recurrent Childhood Pilocytic Astrocytoma Recurrent Childhood Visual Pathway Glioma||Drug: Lenalidomide Other: Pharmacological Study||Phase 2|
I. To determine the objective response rate in children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with Regimen A low-dose (20 mg/m^2/dose) or Regimen B high-dose (115 mg/m^2/dose) lenalidomide.
I. To estimate the event-free survival (EFS) (based on standard two-dimensional tumor measurements, determined by each institution) of children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with lenalidomide.
II. To compare response categories and EFS across the 3 magnetic resonance (MR) sequences (T2-weighted, fluid attenuated inversion recovery [FLAIR], T1-weighted post-contrast).
III. To correlate steady-state pharmacokinetics of lenalidomide (1 sample obtained between days 5-21) with objective response and EFS.
IV. To evaluate toxicities of long-term lenalidomide use.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (Regimen A): Patients receive low-dose lenalidomide 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.
ARM II (Regimen B): Patients receive high-dose lenalidomide 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.
After completion of study treatment, patients are followed up annually for approximately 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas|
|Actual Study Start Date :||March 19, 2012|
|Estimated Primary Completion Date :||March 30, 2019|
Experimental: Arm I (low-dose lenalidomide)
Patients receive low-dose lenalidomide 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: Pharmacological Study
Experimental: Arm II (high-dose lenalidomide)
Patients receive high-dose lenalidomide 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: Pharmacological Study
- Objective response - best response [ Time Frame: Up to 3 years ]The response rate will be calculated as the ratio of the number of patients who demonstrate response (complete response [CR] or partial response [PR]) divided by the number of patients evaluable for response.
- Time to treatment failure (event-free survival [EFS]) [ Time Frame: Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 3 years ]Standard survival methods will be used for analysis of EFS. Analyses include log rank tests and the product-limit (Kaplan-Meier) estimate for estimation of EFS probability.
- Time to death (overall survival [OS]) [ Time Frame: Time from study enrollment to death from any cause, assessed up to 3 years ]Standard survival methods will be used for analysis of OS. Analyses include log rank tests and the product-limit (Kaplan-Meier) estimate for estimation of OS probability.
- Incidence of toxic events defined as one in which a patient has two dose reductions and then experiences another significant toxicity using Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 3 years ]Estimates will be obtained using life-table methods, with an event defined as the first occurrence of a primary toxicity. The rates of individual toxicities in each course of treatment, the number of patients who require a dose reduction and number of patients who come off protocol therapy due to toxicity will be summarized using standard descriptive statistical methods.
- Pharmacokinetic parameters of lenalidomide [ Time Frame: Between days 5-21 of course 1 and each dose reduction ]Correlation of lenalidomide concentration obtained from the steady-state sample and the number of cycles received prior to the occurrence of disease progression will be performed using Pearson's correlation coefficient. Cox regression analysis will be used to assess the association between outcome and steady state levels at a particular cycle.
- Magnetic resonance imaging sequence [ Time Frame: Up to 3 years ]Response categories (complete response, partial response, stable disease, and progression) will be determined from the following three standard magnetic resonance sequences, T2-weighted, fluid attenuated inversion recovery, T1-weighted post-contrast. Percent agreement between the sequences will be estimated as the number of follow-up scans in which the corresponding sequence agreed divided by the total number of follow-up scans. Standard error will be estimated by use of the bootstrap method to account for the correlated dependent response data, and these values will be used to estimate the 95% confidence intervals.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01553149
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|Principal Investigator:||Katherine Warren||Children's Oncology Group|