Protocol Summary

Protocol No.: OCR15982

Sponsor Protocol No.: CC-4047-BRN-001

Study Title
A Phase 2 Clinical Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults with Recurrent or Progressive Primary Brain Tumors

Principal Investigator(s)
Gururangan, Sridharan

This is a Phase 2 multi-center, open-label, parallel-group study that will assess the efficacy, safety and tolerability of pomalidomide in children and young adults aged 1 to

The study will consist of 4 parallel groups, 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 subjects will be enrolled.
Stage 2: If during Stage 1, ≥ 2 subjects achieves either an objective response (either CR or PR) within the first 6 cycles of treatment (within first 3 cycles for DIPG), or a long-term SD, an additional 11 subjects shall be enrolled; otherwise no additional subjects will be enrolled into that group.
If a total of 5 or more subjects across all 20 subjects in a given group (Stage 1 and 2) evaluable for the primary endpoint are observed as having either an objective response (either CR or PR) within the first 6 cycles of treatment (within first 3 cycles for DIPG) or a long-term SD, pomalidomide will be considered effective in that disease indication. Subjects who do not meet the criteria for an objective response or disease progression by the end of Cycle 6 (end of Cycle 3 for DIPG subjects) will be considered as having long-term SD.
Response evaluations will be based on MRI results obtained at each site and will be assessed both locally and by an independent central reviewer. Corticosteroid use and clinical assessments (ie, neurologic status) will also be considered when determining overall response.

Tumor assessments will be conducted by standard MRI with and without contrast using three MRI sequences (T1-weighted pre- and post-contrast, T2-weighted, fluid-attenuated inversion recovery [FLAIR]). Overall radiographic objective response will be assessed utilizing the sequence(s) best representative of tumor in the opinion of the neuroradiologist.

Once treatment has been discontinued, subjects will be followed up for up to 5 years from enrollment of the last subject.

Phase: Phase II

Age Group: Both

Scope: National

Pomalidomide will administered at a starting dose of 2.6 m2/day. Pomalidomide will be provided as either a capsule (0.5 mg, 1 mg, 2 mg, 3 mg or 4 mg) or as an oral suspension (2 mg/mL).

Detailed Eligibility
1. Subject is 1 to 2. Subject (when applicable, parental/legal representative) must understand and voluntarily sign an ICF/IAF prior to any study-related assessments/procedures being conducted.
3. Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
4. Subject has a diagnosis of high-grade glioma, medulloblastoma, ependymoma or Diffuse intrinsic pontine glioma (DIPG) that is recurrent or progressive. Subjects with neurofibromatosis type 1 (NF-1) associated tumors are eligible if the meet all other eligibility criteria.
5. Subject has histological verification of tumor either at the time of diagnosis or recurrence. Subjects with DIPG are exempt from histologic verification if they have typical Magnetic resonance imaging (MRI) findings of DIPG
6. Subject has measurable disease defined as a tumor that is measurable in 2 perpendicular diameters on MRI. For a lesion to be considered measurable, it must be at least twice the slice thickness on MRI (ie, visible on 2 or more axial slices)
7. To document the degree of tumor at study baseline, the following scan(s) must be obtained:
- A brain MRI with and without contrast (ie, gadolinium) and a spine MRI with contrast within 21 days prior to first dose of study treatment. For subjects on steroids, baseline MRI scans must be performed while on stable or decreasing dose of steroids for at least 5 days.
8. Subject has Karnofsky (age >= 16 years) or Lansky (age = 50 at screening
9. Subject has adequate bone marrow function defined as:
- Peripheral Absolute neutrophil count (ANC) >= 1000/mm33
- Platelet count >= 100,000/mm3 (transfusion independent defined as no platelet transfusion within 7 days and recovery from nadir)
- Hemoglobin >= 8 g/dL (red blood cell [RBC] transfusion is allowed)
10. Subject has adequate renal function defined as:
- Adequate real function with Sserum creatinine based on age/gender calculated using the Schwartz formula as described in protocol, or a 24-hour creatinine clearance or radioisotope glomerular filtration rate (GFR) (radioisotope or iothalamate) >= 70 mL/min/1.73 m2.
11. Subject has adequate liver function defined as:
- Total bilirubin = - Alanine aminotransferase (ALT) (SPGT) is = - Serum albumin >= 3 g/dL
12. Subject has adequate pulmonary function defined as:
- No evidence of dyspnea at rest
- A pulse oximetry >= 93%
13. Subject has recovered from clinically significant acute treatment related toxicities from all prior therapies. Recovery is defined as a toxicity Grade =14. Subject has no significant worsening in clinical status for a minimum of 7 days prior to first dose of study drug.
15. Subject (and when applicable, with parental/legal representative) is willing and able to adhere to the study visit schedule and other protocol requirements.
16. Females of Childbearing Potential (FCBP) and male subjects who have reached puberty (and when applicable, with parental/legal representative) must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction.

1. Subject has a history of non-central line related thrombosis (arterial or venous), more than one prior central-line related thrombosis or known coagulopathy.
2. Subject has first degree family member with a known hereditary coagulopathy.
3. Subject is actively on anticoagulation therapy.

** Contact study team for complete eligibility details

Applicable Disease Sites
Brain and Nervous System
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville

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