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

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of CC-90010 when combined with standard of care treatment, temozolomide (TMZ) with or without radiotherapy (RT) in the newly diagnosed WHO Grade IV glioblastoma (ndGBM).

Official Title
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A Phase 1b, Open-label, Dose-Finding Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Subjects With Newly Diagnosed Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: CC-90010
* Drug: Temozolomide
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary isocitrate dehydrogenase (IDH)-wild type newly diagnosed World Health Organization (WHO) Grade IV Glioblastoma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status must be available prior to randomization Karnofsky performance status of ≥70 Exclusion Criteria: Indeterminate MGMT promoter methylation status Biopsy only of glioblastoma (GBM) at surgery, defined as < 20% resection of enhancing tumor Any known metastatic extracranial or leptomeningeal disease Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br> | Drug: CC-90010<br>* Specified dose on specified days<br>Drug: Temozolomide<br>* Specified dose on specified days<br>Radiation: Radiotherapy<br>* Specified dose on specified days<br>|
| Experimental: Part B - CC-90010 + Temozolomide (TMZ) + Radiotherapy (RT)<br> | Drug: CC-90010<br>* Specified dose on specified days<br>Drug: Temozolomide<br>* Specified dose on specified days<br>Radiation: Radiotherapy<br>* Specified dose on specified days<br>|
| Other: Part B - Standard TMZ + RT<br>Control | Radiation: Radiotherapy<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | Parts A and B | Up to 3 years | 
| Incidence of serious adverse events (SAEs) using the NCI CTCAE v5.0 | Parts A and B | Up to 3 years | 
| Incidence of dose-limiting toxicities (DLTs) | Part A | Up to 3 years | 
| Maximum Tolerated Dose (MTD) of CC-90010 in combination with Temozolomide (TMZ) | Part A | Up to 3 years | 
| MTD of CC-90010 in combination with TMZ and Radiation Therapy (RT) | Part A | Up to 3 years | 
| Recommended Phase 2 Dose (RP2D) of CC-90010 in combination with TMZ | Part A | Up to 3 years | 
| RP2D of CC-90010 in combination with TMZ and RT | Part A | Up to 3 years | 
| Median Progression-free survival (PFS) in Arm A vs Arm B | Part B | Up to 12 months | 
| Hazard ratio for PFS in Arm A vs Arm B | Part B | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) defined as the time from the first dose of CC-90010 to the first occurrence of disease progression or death from any cause | Parts A and B | Up to 5 years | 
| Overall survival (OS) measured as the time from the first dose of CC-90010 to death due to any cause and will be analyzed in a manner similar to that described for PFS | Parts A and B | Up to 5 years | 
| Duration of therapy (DoT) in Arm A vs Arm B | Part B | Up to 5 years | 
| Response by Response Assessment in Neuro-Oncology (RANO) criteria | Parts A and B | Up to 5 years | 
| Pharmacokinetics - Maximum observed plasma concentration (Cmax) | Parts A and B | Up to 2 years | 
| Pharmacokinetics - Area under the plasma concentration time-curve (AUC) | Parts A and B | Up to 2 years | 
| Pharmacokinetics - Time to maximum plasma concentration (Tmax) | Parts A and B | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-90010, Temozolomide, Glioblastoma, NEWLY DIAGNOSED, Radiation therapy, Safety, Tolerability, MTD and RP2D