Low-Dose or High-Dose Lenalidomide in Treating Younger Patients with Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Under 22||ACNS1022|
NCI-2012-00703, CDR0000728296, COG-ACNS1022, NCT01553149
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.
Further Study Information
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.
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
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
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
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)
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
All patients and/or their parents or legal guardians must sign a written informed consent
No evidence of dyspnea at rest and a pulse oximetry > 94% if there is clinical indication for determination
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
Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
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 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)
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 a body surface area (BSA) >= 0.4 m^2 at the time of study enrollment
Platelet count >= 100,000/uL (transfusion independent)
Patients must be able to swallow intact capsules
Steroids: patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to baseline MRI
Growth factor(s): must not have received within 2 weeks of entry onto this study
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Peripheral absolute neutrophil count (ANC) >= 1,000/uL
Serum albumin >= 2 g/dL
Patients must have histologic verification of malignancy; histologic confirmation for patients with optic pathway gliomas will not be required
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
- Cervical cap
The two methods of birth control requirement applies to all sexually active females unless they have undergone a hysterectomy or bilateral oophorectomy
Patients with a significant systemic illness that is not well-controlled in the opinion of the treating physician 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 who have an uncontrolled or untreated infection are not eligible
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
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 who are pregnant are not eligible
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
Patients with a history of thromboembolism unrelated to a central line, or patients with a known predisposition syndrome for thromboembolism are not eligible
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
National Cancer Institute
- National Cancer Institute
Royal Brisbane and Women's Hospital
Timothy Edward George Hassall
Timothy Edward George Hassall
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01553149
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.