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

Study ID
NCI-2012-00703

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Ryan Carstens
214/648-4916
ryan.carstens@childrens.com

Principal Investigator
Daniel Bowers, M.D.

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

Brief Overview


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.

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 study treatment, patients are followed up annually for approximately 3
years.

Participant Eligibility


Inclusion Criteria:

- Patients must have a body surface area (BSA) >= 0.4 m^2 at the time of study
enrollment

- Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed,
progressed, or become refractory to conventional therapy; patients with
neurofibromatosis (NF-1) are eligible

- Patients must have histologic verification of malignancy; histologic confirmation for
patients with optic pathway gliomas will not be required

- Patients must have measurable residual disease, defined as tumor that is measurable
in two perpendicular diameters on magnetic resonance imaging (MRI); for a lesion to
be considered measurable, it must be at least twice the slice thickness on MRI (i.e.
visible on more than one slice)

- To document the degree of residual tumor, the following must be obtained:

- All patients must have a brain MRI with and without contrast (gadolinium) within
1 week prior to study enrollment; for patients on steroids, baseline MRI scans
must be performed after at least 1 week at a stable or decreasing dose of
steroids

- All patients with a history of spinal or leptomeningeal disease, and those
patients with symptoms suspicious of spinal disease, must have a spine MRI with
and without contrast (gadolinium) performed within 2 weeks prior to study
enrollment

- Patients must have a Lansky or Karnofsky performance status score of >= 60%; use
Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

- Patients must have been treated with at least one prior treatment regimen that
included carboplatin; patients who have received prior radiation therapy for this
tumor are eligible

- Patients must have recovered (to Common Toxicity Criteria [CTC] version [v.]4.0 =<
grade 1 unless indicated below) from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study, with the
exception of alopecia, weight changes and grade I or II lymphopenia

- Myelosuppressive chemotherapy: must not have received within 3 weeks of entry
onto this study (6 weeks if prior nitrosourea or mitomycin-C)

- Biologic (anti-neoplastic agent): at least 7 days after the last dose of a
biologic agent; for agents that have known adverse events occurring beyond 7
days after administration, this period must be extended beyond the time during
which adverse events are known to occur

- Immunotherapy: at least 42 days after the completion of any type of
immunotherapy, e.g. tumor vaccines

- Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose
of a monoclonal antibody

- Radiation therapy (RT): patients must have had their last fraction of
craniospinal RT >= 6 months prior to study entry and their last fraction of
focal RT >= 4 weeks prior to study entry; if the lesion used for on-study
criteria is in the radiation field, there must be evidence of tumor progression
after radiation therapy was completed

- Study specific limitations on prior therapy:

- Patients who have received thalidomide are eligible if all acute
thalidomide-related toxicity has resolved

- Patients must not have received lenalidomide previously

- Growth factor(s): must not have received within 2 weeks of entry onto this study

- Steroids: patients who are receiving corticosteroids must be on a stable or
decreasing dose for at least 1 week prior to baseline MRI

- Peripheral absolute neutrophil count (ANC) >= 1,000/uL

- Platelet count >= 100,000/uL (transfusion independent)

- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

- Creatinine clearance or radioisotope glomerular filtration rate(GFR) >= 70 mL/min/m^2
OR a serum creatinine based on age/gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110
U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

- Serum albumin >= 2 g/dL

- No evidence of dyspnea at rest and a pulse oximetry > 94% if there is clinical
indication for determination

- Patients must be able to swallow intact capsules

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Exclusion Criteria:

- Female patients who are pregnant are not eligible

- Lactating females are not eligible unless they have agreed not to breastfeed their
infants while receiving protocol therapy and for 28 days after the last dose of
lenalidomide

- Female patients of childbearing potential are not eligible unless they commit to
complete abstinence or have been on 2 methods of birth control, including 1 highly
effective method and 1 additional method at the same time (unless committing to
complete abstinence of heterosexual intercourse) at least 28 days (4 weeks) prior to
study enrollment; sexually active females must also agree to remain on 2 methods of
birth control, during treatment (including during dose interruptions), and continuing
for at least 28 days after the completion of protocol therapy; examples of methods of
contraception are as follows:

- Highly effective methods (must use at least 1):

- Intrauterine device (IUD)

- Hormonal (prescription birth control pills, injections, implants)

- Tubal ligation

- Partner's vasectomy

- Additional effective methods:

- Male condom

- Diaphragm

- Cervical cap The two methods of birth control requirement applies to all
sexually active females unless they have undergone a hysterectomy or
bilateral oophorectomy

- Female patients of childbearing potential (including those who commit to complete
abstinence) are not eligible unless they agree to ongoing pregnancy testing and
counseling every 28 days about pregnancy precautions and risks of fetal exposure

- Male patients of child fathering potential are not eligible unless they have agreed
to use latex condoms during intercourse with a woman of childbearing potential while
receiving treatment and for 28 days thereafter

- Patients with a history of thromboembolism unrelated to a central line, or patients
with a known predisposition syndrome for thromboembolism are not eligible

- Patients who have an uncontrolled or untreated infection are not eligible

- Patients with known overt cardiac disease, including but not limited to a history of
myocardial infarction, severe or unstable angina, clinically significant peripheral
vascular disease, grade 2 or greater heart failure, or serious and inadequately
controlled cardiac arrhythmia are not eligible

- Patients with a significant systemic illness that is not well-controlled in the
opinion of the treating physician are not eligible