Brief Summary
The purpose of this study is to see if combining silevertinib with temozolomide after surgery and radiotherapy helps treat newly diagnosed glioblastoma (GBM) better than using temozolomide alone in the maintenance setting.
Specifically, this study is being done to find answers to the following questions:
* How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM?
* What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)?
* Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?
Specifically, this study is being done to find answers to the following questions:
* How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM?
* What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)?
* Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?
Brief Title
Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII
Detailed Description
Silevertinib was designed to block a growth signal important to some cancers where tumors grow because of changes in a protein called epidermal growth factor receptor (EGFR). These changes are called gene amplifications, mutations, or alterations and are found in tumors. Temozolomide is a drug that fights cancer cells by damaging DNA (the genetic material of cells), which could cause the tumor cells to die. It is the standard treatment for adults with certain types of newly diagnosed brain cancer, like GBM. It is given together with radiotherapy and sometimes afterward as maintenance therapy.
This study has 2 parts. To be eligible for the study, participants must have received a diagnosis of GBM, had surgery to remove or reduce the size of the tumor, and received adjuvant radiation therapy and temozolomide. No other prior treatments for GBM are allowed.
In Part 1 (called the Safety Lead-in), participants will receive silevertinib combined with temozolomide to determine if the combination is safe and to find the best dose. Approximately 12 participants are expected to enroll in Part 1 of the study.
In Part 2, all participants will be randomized to one of two different treatment groups:
* Group 1: Silevertinib + temozolomide
* Group 2: Temozolomide only
Approximately 150 participants are expected to be randomized in Part 2 of the study.
In both Part 1 and Part 2, the study treatment will be given in "cycles". Each cycle will be 28 days. After a cycle ends, the next cycle will immediately begin the next day. Both silevertinib and temozolomide will be taken orally. Silevertinib is taken daily until disease progression and temozolomide is taken for the first 5 days of each cycle (up to 6 cycles).
If participants are found to be eligible for the study and enrolled (in Part 1) or randomized (in Part 2), participants will:
* Take the study drug as directed
* Return for frequent clinic visits to monitor overall health and status of GBM
* Undergo imaging and other laboratory tests to determine status of GBM
* Complete a paper diary at home to record the date and time(s) that the study drug is taken
This study has 2 parts. To be eligible for the study, participants must have received a diagnosis of GBM, had surgery to remove or reduce the size of the tumor, and received adjuvant radiation therapy and temozolomide. No other prior treatments for GBM are allowed.
In Part 1 (called the Safety Lead-in), participants will receive silevertinib combined with temozolomide to determine if the combination is safe and to find the best dose. Approximately 12 participants are expected to enroll in Part 1 of the study.
In Part 2, all participants will be randomized to one of two different treatment groups:
* Group 1: Silevertinib + temozolomide
* Group 2: Temozolomide only
Approximately 150 participants are expected to be randomized in Part 2 of the study.
In both Part 1 and Part 2, the study treatment will be given in "cycles". Each cycle will be 28 days. After a cycle ends, the next cycle will immediately begin the next day. Both silevertinib and temozolomide will be taken orally. Silevertinib is taken daily until disease progression and temozolomide is taken for the first 5 days of each cycle (up to 6 cycles).
If participants are found to be eligible for the study and enrolled (in Part 1) or randomized (in Part 2), participants will:
* Take the study drug as directed
* Return for frequent clinic visits to monitor overall health and status of GBM
* Undergo imaging and other laboratory tests to determine status of GBM
* Complete a paper diary at home to record the date and time(s) that the study drug is taken
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(866) 955-4397
Central Contact Email
blackdiamondtx@careboxhealth.com
Completion Date
Completion Date Type
Estimated
Conditions
GLIOBLASTOMA (GBM)
NEWLY DIAGNOSED GLIOBLASTOMA
GBM
GLIOBLASTOMA MULTIFORME (GBM)
GLIOMA
CENTRAL NERVOUS SYSTEM DISEASES
BRAIN CANCER
Eligibility Criteria
Key Inclusion Criteria:
* Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
* Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
* For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
* For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
* For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
* No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
* At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression.
Key Exclusion Criteria:
* Recurrent multifocal disease, metastatic, leptomeningeal, or extracranial GBM, or gliomatosis cerebri.
* Progression of GBM prior to Enrollment, Screening, or Randomization.
* Biopsy-only/no resectional surgery.
* Prior or concomitant treatment for GBM with an EGFR-targeting agent, including silevertinib, bevacizumab, cytotoxic chemotherapy, immunotherapy, experimental therapies, Gliadel wafers, GammaTile®, or other intratumoral or intracavitary antineoplastic therapy.
* Intent to use Optune® (TTF).
* Significant other uncontrolled health conditions or other malignancies.
* Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
* Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
* For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
* For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
* For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
* No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
* At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression.
Key Exclusion Criteria:
* Recurrent multifocal disease, metastatic, leptomeningeal, or extracranial GBM, or gliomatosis cerebri.
* Progression of GBM prior to Enrollment, Screening, or Randomization.
* Biopsy-only/no resectional surgery.
* Prior or concomitant treatment for GBM with an EGFR-targeting agent, including silevertinib, bevacizumab, cytotoxic chemotherapy, immunotherapy, experimental therapies, Gliadel wafers, GammaTile®, or other intratumoral or intracavitary antineoplastic therapy.
* Intent to use Optune® (TTF).
* Significant other uncontrolled health conditions or other malignancies.
Inclusion Criteria
Inclusion Criteria:
* Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
* Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
* For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
* For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
* For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
* No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
* At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression.
* Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
* Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
* For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
* For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
* For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
* No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
* At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression.
Gender
All
Gender Based
false
Keywords
EGFR
Glioblastoma
Unmethylated
Unmethylated MGMT promoter
Newly Diagnosed
temozolomide
Temodar
silevertinib
BDTX-1535
EGFR alterations
epidermal growth factor receptor
EGFRvIII
epidermal growth factor receptor (EGFR)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07326566
Org Class
Industry
Org Full Name
Black Diamond Therapeutics, Inc.
Org Study Id
BDTX-1535-201
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2 Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Silevertinib, an Oral EGFR Inhibitor, in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma With Unmethylated MGMT Promoter and EGFRvIII
Primary Outcomes
Outcome Description
Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.
Outcome Measure
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
Outcome Time Frame
12 months
Secondary Outcomes
Outcome Description
Overall survival defined as time from first dose of study drug to death from any cause.
Outcome Time Frame
18 months
Outcome Measure
Overall Survival
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Adilia Hormigo
Investigator Email
adilia.hormigo@einsteinmed.edu
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Brain, Spinal Cord & Nervous System --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- BRAIN NEOPLASMS
Cancer --- NEOPLASMS
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- CENTRAL NERVOUS SYSTEM NEOPLASMS
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Brain, Spinal Cord & Nervous System --- BRAIN DISEASES
MeSH Terms
GLIOBLASTOMA
GLIOMA
CENTRAL NERVOUS SYSTEM DISEASES
BRAIN NEOPLASMS
ASTROCYTOMA
NEOPLASMS, NEUROEPITHELIAL
NEUROECTODERMAL TUMORS
NEOPLASMS, GERM CELL AND EMBRYONAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS, NERVE TISSUE
NERVOUS SYSTEM DISEASES
CENTRAL NERVOUS SYSTEM NEOPLASMS
NERVOUS SYSTEM NEOPLASMS
NEOPLASMS BY SITE
BRAIN DISEASES
TEMOZOLOMIDE
DACARBAZINE
TRIAZENES
ORGANIC CHEMICALS
IMIDAZOLES
AZOLES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS