This study will assess the efficacy, safety and tolerability of pomalidomide in children and young adults aged 1 to \< 21 years with recurrent or progressive primary brain tumors in one of four primary brain tumor types: high-grade glioma (HGG), medulloblastoma, ependymoma and diffuse intrinsic pontine glioma (DIPG).
The study will consist of 4 parallel groups of participants, one for each of the following primary brain tumor types: high-grade glioma, medulloblastoma, ependymoma and DIPG. A Simon's Optimal two-stage study design will be applied to each group and enrollment will occur as follows: * Stage 1: Nine participants will be enrolled in each brain tumor type group * Stage 2: If during Stage 1, ≥ 2 participants achieves either an objective response (either complete response or partial response) within the first 6 cycles of treatment (or within the first 3 cycles for DIPG participants), or a long-term stable disease, an additional 11 participants shall be enrolled; otherwise no additional participants will be enrolled into that group. * If a total of 5 or more participants across all 20 participants in a given group (Stage 1 and 2) evaluable for the primary endpoint are observed as having either an objective response (either complete response or partial response) within the first 6 cycles of treatment (or within the first 3 cycles for DIPG participants) or a long-term stable disease, pomalidomide will be considered effective in that disease indication. Once treatment has been discontinued, participants will be followed up for up to 5 years from enrollment of the last participant. Participants who withdraw from either stage for reasons other than disease progression prior to completing Cycle 1 of study treatment will be replaced.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
: Subjects will be administered pomalidomide on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle and will continue treatment for up to 24 cycles or until disease progression, withdrawal of consent/assent or unresolved toxicities as described in the protocol.
Pomalidomide will be provided as gelatin capsules and as an oral suspension. The starting dose will be 2.6 mg/m²/day, administered on Days 1 to 21, followed by a 7-day rest period, of each 28-day treatment cycle.
Stanford University Cancer Center
Stanford, California, United States
University Of Florida
Gainesville, Florida, United States
Percentage of Participants With an Objective Response and Long-term Stable Disease
The percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of \< 50% or an increase of \< 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
Percentage of Participants Who Achieved an Objective Response (ORR)
Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
Percentage of Participants With Long-term Stable Disease
Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or \> 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of \< 50% or an increase of \< 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
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Ann and Robert H Lurie Childrens Hospital of Chicago
Chicago, Illinois, United States
Local Institution - 506
Bethesda, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Texas Children's Hospital
Houston, Texas, United States
Local Institution - 104
Lille, Nord, France
Local Institution - 102
Lyon, France
Local Institution - 103
Marseille, France
Local Institution - 100
Paris, France
...and 12 more locations
Time frame: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
Duration of Response (DoR)
DoR is defined as the time from the date of the first objective response (complete response \[CR\] or partial response \[PR\]) to disease progression. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size.
Time frame: From the first dose of pomalidomide to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 71 months)
Kaplan-Meier Estimate of Progression-Free Survival (PFS)
Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive.
Time frame: From the first dose of pomalidomide to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 71 months)
Kaplan-Meier Estimate of Overall Survival (OS)
Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
Time frame: From the first dose of pomalidomide to the date of death due to any cause (Up to 71 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug.
Time frame: From the first dose of pomalidomide until 28 days after the last dose (Up to approximately 72 months)