| Eligibility |
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
1. Men and women = 18 years of age,) with recurrent or progressive WHO Grade II Diffuse
Astrocytoma, Grade III Anaplastic Astrocytoma or recurrent WHO Grade IV Glioblastoma .
2. Subjects must have previously completed standard or a hypofractionated course of
radiation therapy and have been exposed to procarbazine, lomustine and vincristine
(for Grade II Astrocytoma), including those who have progressed on (or not been able
to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer
therapy, with radiation completed > 12 weeks prior to the first CC-90010 dose (Day 1).
3. Subject must be in first or second recurrence.
4. Subject must have archival tumor tissue suitable for genetic testing and must give
permission to access and test the tissue.
5. Subject is considered an appropriate candidate for surgical resection of the recurrent
tumor tissue (salvage resection).
6. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.
7. Subject must meet laboratory values at screening:
- Absolute neutrophil count (ANC) = 1.5 x 10^9/L without growth factor support for
7 days (14 days if subject received pegfilgrastim).
- Hemoglobin (Hgb) =10 g/dL
- Platelet count (plt) =100 x 10^9/L
- Serum potassium concentration within normal range, or correctable with
supplements
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x Upper
Limit of Normal (ULN).
- Serum total bilirubin = 1.5 x ULN.
- Serum creatinine = 1.5 x ULN or measured glomerular filtration rate (GFR) = 50
mL/min/1.73 m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr
EDTA or 1 iothalamate, or creatinine clearance of = 50 mL/min using
Cockroft-Gault equation.
- Serum albumin > 3.5 g/dL
- PT (or INR) and APTT = normal range
8. Females and males must agree to contraceptive methods and avoid conceiving throughout
study and up to 46 days (females) and 106 days (males) following last dose of
CC-90010.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. Subject has received anti-cancer therapy (either approved or investigational) within =
4 weeks (6 weeks for nitrosoureas) or 5 half-lives, whichever is shorter, prior to
starting CC-90010. If subject received prior immunotherapy (immune checkpoint
inhibitor, vaccine, etc.), a 2 week wash-out is required. For a subject treated with
the Optune-TTF device, a 2 day period without use is required.
2. Toxicities resulting from prior chemotherapy, surgery, or radiotherapy must have
resolved to = NCI CTCAE (version 5.0) Grade 1 prior to starting CC-90010 treatment
(with the exception of Grade 3 alopecia).
3. Subject has undergone major surgery = 4 weeks or minor surgery = 2 weeks prior to
starting CC-90010 or subject who has not recovered from surgery.
4. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue
or inflammatory bowel disease) = NCI CTCAE Grade 2, despite medical management, or any
other significant GI disorder that could affect the absorption of CC-90010.
5. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly
those with a history of and/or risk of perforation and GI tract hemorrhages.
6. Evidence of CNS hemorrhage on baseline MRI or CT scan (except for post-surgical,
asymptomatic Grade 1 hemorrhage that has been stable for at least 4 weeks).
7. Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral
edema within 7 days of study therapy.
8. Known symptomatic acute or chronic pancreatitis.
9. Impaired cardiac function or clinically significant cardiac diseases, including any of
the following:
- LVEF < 45% as determined by multiple gated acquisition scan (MUGA) or
echocardiogram (ECHO).
- Complete left bundle branch or bifascicular block.
- Congenital long QT syndrome.
- Persistent or clinically meaningful ventricular arrhythmias or atrial
fibrillation.
- QTcF = 480 msec on Screening ECG (mean of triplicate recordings); a marked
baseline prolongation of QT/QTc interval, using Fridericia´s QT correction
formula.
- History of additional risk factors for Torsade de Pointes (TdP) (e.g. heart
failure, hypokalemia, family history of Long QT syndrome.
- Use of concomitant medications that prolong the QT/QTc interval.
- Unstable angina pectoris or myocardial infarction = 6 months prior to starting
CC-90010.
- Other clinically significant heart disease such as congestive heart failure
requiring treatment or uncontrolled hypertension (blood pressure = 160/95 mm Hg).
10. Pregnant or nursing females.
11. Known HIV infection.
12. Known chronic active hepatitis B or C virus (HBV, HCV) infection.
13. Subject with a requirement for ongoing treatment with therapeutic dosing of
anticoagulants or for ongoing prophylactic anticoagulation. Low dose low molecular
weight heparin for catheter maintenance is allowed.
14. History of concurrent second cancers requiring active, ongoing systemic treatment.
15. Evidence of history of bleeding diathesis.
16. Subject with known prior episodes of non-arteritic anterior ischemic optic neuropathy
(NAION) should be excluded from the study. CC-90010 should be used with caution in
subjects with retinitis pigmentosa.
17. Subject has any significant medical condition (e.g., active or uncontrolled infection
or renal disease), laboratory abnormality, or psychiatric illness that would prevent
the subject from participating (or compromise compliance) in the study or would place
the subject at unacceptable risk if he/she were to participate in the study.
18. Subject has any condition that confounds the ability to interpret data from the study.
19. Subject with poor bone marrow reserve as assessed by Investigator such as in the
following condition:
• Requiring regular hematopoietic support (blood or platelet transfusions,
erythropoietin, granulocyte colony stimulating factor [GCSF] or other hematopoietic
growth factors)
20. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20
days for severe/critical illness prior to starting study drug.
• Acute symptoms must have resolved and based on investigator assessment in
consultation with the medical monitor, there are no sequelae that would place the
participant at a higher risk of receiving study treatment.
21. Previous SARS-CoV-2 vaccine within 14 days of starting drug study.
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