Clinical Trial: Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathwa

Brief Summary: This randomized phase II trial studies how well low-dose lenalidomide works compared with high-dose lenalidomide in treating younger patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas that have come back (recurrent), have not responded to treatment (refractory), or are growing, spreading, or getting worse (progressive). Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether low-dose lenalidomide is more or less effective than high-dose lenalidomide in treating patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective response - best response [ Time Frame: Up to 3 years ]

Original Primary Outcome: Objective response - best overall response (complete or partial response) at any time on the study

Current Secondary Outcome:

• 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 4.0 [ 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.
• MRI sequence [ Time Frame: Up to 3 years ]
  Response categories (CR, PR, stable disease, and progression) will be determined from the following three standard MR sequences, T2-weighted, FLAIR, 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.
• 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.
• 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.
• Time to treatment failure (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.

Original Secondary Outcome:

• Time to treatment failure (EFS), time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm
• Time to death (Overall survival [OS]) - the time from study enrollment to death from any cause
• Toxicity events using Common Terminology Criteria for Adverse Events (CTCAE) version 4
• Correlation of steady-state pharmacokinetic levels of lenalidomide with best response and EFS at the patient dose

Dates:
Date Received: March 10, 2012
Date Started: March 2012
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017