A Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Subjects With Newly Diagnosed Glioblastoma

• Status: Recruiting
• Trial end date: 2024-11-20
• Target enrollment: 0
• Participant gender: All

Summary

Study CC-90010-GBM-002 is for newly diagnosed WHO Grade IV glioblastoma to determine the safety and tolerability and evaluate escalating doses of the investigational drug CC-90010 when combined with standard of care treatment temozolomide (TMZ) with or without radiotherapy (RT).

The standard of care for ndGBM includes surgical resection to the extent that is safely feasible, followed by RT plus concomitant TMZ chemotherapy, and up to 6 months of adjuvant TMZ. The study also aims to determine whether the addition of CC-90010 can control the disease.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celgene
• Treatments: Temozolomide

Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study criteria:

1. Males and females of ≥ 18 years of age at the time of signing the informed consent form (ICF).

2. Newly diagnosed, histologically confirmed WHO Grade IV Glioblastoma and must have undergone complete or partial tumor resection.

3. Toxicities resulting from surgery must have resolved to NCI CTCAE (v5.0) Grade ≤ 1 prior to starting CC-90010 treatment (with the exception of Grade 2 alopecia).

4. For Concomitant Therapy: Prior tumor resection up to 8 weeks prior to the first dose of CC-90010.

5. For Adjuvant Therapy: Subject must have recently completed standard or a hypofractionated course of radiotherapy with TMZ chemotherapy, and then have an MRI documenting stable disease prior to the first dose of CC 90010.

6. For Adjuvant Therapy:

1. All AEs resulting from prior RT+TMZ chemotherapy must have resolved to NCI CTCAE (v5.0) Grade 1 (except for laboratory parameters outlined below).

2. Subject must have not experienced significant toxicity to prior RT+TMZ (i.e., Grade 4 hematological toxicity)

3. Subject must have received at least 80% of the planned standard doses of RT and/or TMZ administered throughout the 42 day concomitant period (up to 49 days).

7. Subject with archival tumor tissue suitable for molecular genetic testing must give permission to access and test the tissue.

8. Life expectancy of at least 3 months.

9. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1.

10. Subject must have the following laboratory values at screening:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if subject received pegfilgrastim).

2. Hemoglobin (Hgb) ≥10 g/dL

3. Platelet count (plt) ≥150 x 109/L

4. Serum potassium concentration within normal range, or correctable with supplements

5. Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamate pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≤ 3.0 x Upper Limit of Normal (ULN).

6. Serum total bilirubin ≤ 1.5 x ULN.

7. 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 1125 iothalamate, or creatinine clearance of ≥ 50 mL/min using Cockroft-Gault equation.

8. Serum albumin > 3.5 g/dL

9. PT (or INR) and APTT within normal range

11. Females of childbearing potential (FCBP) and men with partners of child bearing potential must agree to take contraceptive measures for duration of treatment and for at least 46 days after last dose of CC-90010 for females and for 106 days after last dose of CC-90010 for males, and for 180 days after last dose of Temozolomide for both males and females

12. Males must agree to refrain from donating semen while on study drug and for 106 days after discontinuation of CC-90010 or 180 days after the last dose of TMZ, whichever is longer.

13. Females must agree to refrain from donating ova while on study treatment and for 46 days after the last dose of CC-90010 or 180 days after the last dose of TMZ, whichever is longer.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Prior chemotherapy or other anti-tumor treatment for GBM (either approved or investigational) except for surgery and for the Adjuvant Therapy cohort, mandatory concomitant TMZ+RT.

2. 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.

3. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.

4. Evidence of recent, symptomatic CNS hemorrhage on baseline MRI or CT scan.

5. Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral edema within 14 days prior to the first dose of CC-90010.

6. Known symptomatic acute or chronic pancreatitis.

7. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

• LVEF < 45% as determined by multiple gated acquisition (MUGA) scan 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 milliseconds (msec) on Screening ECG (mean of triplicate recordings); a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 msec (CTCAE Grade ≥ 2), using Fridericia's QT correction formula.

• A history of additional risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

• The use of concomitant medications that prolong the QT/QTc interval.

• Unstable angina 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).

8. Pregnant or nursing females.

9. Known HIV infection.

10. Known chronic active hepatitis B or C virus (HBV, HCV) infection.

• Subjects who are seropositive due to HBV vaccination are eligible.

• Subjects who have no active viral infection and are under adequate prophylactics against HBV re-activation are eligible.

11. Subject with a requirement for ongoing treatment with therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin antagonists), or for ongoing prophylactic anticoagulation. Low dose low molecular weight heparin for catheter maintenance is allowed.

12. History of concurrent second cancers requiring active and ongoing systemic treatment, except non-melanoma skin cancer, completely resected cervical carcinoma in situ, low risk prostate cancer (cT1-2a N0 and Gleason score ≤ 6 and PSA < 10 ng/mL), either totally resected or irradiated with curative intent (with PSA of less than or equal to 0.1 ng/mL) or under active surveillance. Other cancers for which the subject has completed potentially curative treatment more than 3 years prior to study entry are allowed.

13. Evidence of history of bleeding diathesis. Any hemorrhage/bleeding event > CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose of CC-90010.

14. 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.

15. Subject has any significant medical condition (e.g., active or uncontrolled infection, hepatic 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.

16. Subject has any condition that confounds the ability to interpret data from the study.

17. Subject with poor bone marrow reserve as assessed by Investigator such as in conditions requiring regular hematopoietic support (blood or platelet transfusions, erythropoietin, granulocyte colony stimulating factor [GCSF] or other hematopoietic growth factors).