Ignite Creation Date:
2024-05-06 @ 2:40 PM
Last Modification Date:
2024-10-26 @ 1:35 PM
Study NCT ID:
NCT04396860
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-23
First Post:
2020-05-20
Brief Title:
Testing the Use of the Immunotherapy Drugs Ipilimumab and Nivolumab Plus Radiation Therapy Compared to the Usual Treatment Temozolomide and Radiation Therapy for Newly Diagnosed MGMT Unmethylated Glioblastoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Randomized Phase IIIII Open-Label Study of Ipilimumab and Nivolumab Versus Temozolomide in Patients With Newly Diagnosed MGMT Tumor O-6-Methylguanine DNA Methyltransferase Unmethylated Glioblastoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase IIIII trial compares the usual treatment with radiation therapy and temozolomide to radiation therapy in combination with immunotherapy with ipilimumab and nivolumab in treating patients with newly diagnosed MGMT unmethylated glioblastoma Radiation therapy uses high energy photons to kill tumor and shrink tumors Chemotherapy drugs such as temozolomide work in different ways to stop the growth of tumor cells either by killing the cells by stopping them from dividing or by stopping them from spreading Temozolomide may not work as well for the treatment of tumors that have the unmethylated MGMT Immunotherapy with monoclonal antibodies called immune checkpoint inhibitors such as ipilimumab and nivolumab may help the bodys immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread It is possible that immune checkpoint inhibitors may work better at time of first diagnosis as opposed to when tumor comes back Giving radiation therapy with ipilimumab and nivolumab may lengthen the time without brain tumor returning or growing and may extend patients life compared to usual treatment with radiation therapy and temozolomide
Detailed Description:
PRIMARY OBJECTIVES
I To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs progression-free survival PFS versus adding temozolomide to radiotherapy in patients with newly diagnosed glioblastoma GBM without MGMT promoter methylation Phase II II To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs overall survival OS versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation Phase III
SECONDARY OBJECTIVES
I To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs PFS versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation for the phase III part of the study
II To determine if adding ipilimumab and nivolumab to radiotherapy significantly increases the 2-year OS rate versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation
III To evaluate the safety of adding ipilimumab and nivolumab to radiotherapy via comparative frequency between arms of specific adverse events of interest and frequency summaries for all adverse event types
IV To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on patient reported outcomes PROs as measured by the MD Anderson Symptom Inventory - Brain Tumor MDASI-BT in patients with newly diagnosed GBM without MGMT promoter methylation
V To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on selected Patient Reported Outcomes-Common Terminology Criteria for Adverse Events PRO-CTCAE items in patients with newly diagnosed GBM without MGMT promoter methylation
VI To evaluate the impact of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on neurocognitive function NCF in patients with newly diagnosed GBM without MGMT promoter methylation
EXPLORATORY OBJECTIVES
I To explore biomarkers in pre-treatment archival tumor tissue that may predict efficacy of ipilimumab and nivolumab as measured by OS PFS and 2-year OS rate such as but not limited to
Ia PDL1 expression Ib Mutational burden II To explore in the two treatment separately whether the MGMT protein expression correlates with clinical outcomes including OS PFS and 2-year OS rate
III To evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms
OUTLINE Patients are randomized to 1 of 2 arms
ARM 1 Patients undergo radiation therapy for 5 days per week Monday-Friday for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide orally PO daily for 6 weeks After radiation patients may wear the Optune device at the discretion of the patient and their treating physician Beginning 1 month after radiation therapy patients receive temozolomide on days 1-5 Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity Patients also undergo contrast-enhanced brain magnetic resonance imaging MRI throughout the trial
ARM 2 Patients undergo radiation therapy for 5 days per week Monday-Friday for a total of 30 fractions over 6 weeks Starting on the first day of radiation patients also receive ipilimumab intravenously IV over 90 minutes once every 4 weeks Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression Patients also undergo contrast-enhanced brain MRI throughout the trial
After completion of study treatment patients are followed up every 3 months for year 1 then every 4 months for year 2 and then every 6 months thereafter
I To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs progression-free survival PFS versus adding temozolomide to radiotherapy in patients with newly diagnosed glioblastoma GBM without MGMT promoter methylation Phase II II To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs overall survival OS versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation Phase III
SECONDARY OBJECTIVES
I To determine if adding ipilimumab and nivolumab to radiotherapy significantly prolongs PFS versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation for the phase III part of the study
II To determine if adding ipilimumab and nivolumab to radiotherapy significantly increases the 2-year OS rate versus adding temozolomide to radiotherapy in patients with newly diagnosed GBM without MGMT promoter methylation
III To evaluate the safety of adding ipilimumab and nivolumab to radiotherapy via comparative frequency between arms of specific adverse events of interest and frequency summaries for all adverse event types
IV To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on patient reported outcomes PROs as measured by the MD Anderson Symptom Inventory - Brain Tumor MDASI-BT in patients with newly diagnosed GBM without MGMT promoter methylation
V To evaluate the effect of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on selected Patient Reported Outcomes-Common Terminology Criteria for Adverse Events PRO-CTCAE items in patients with newly diagnosed GBM without MGMT promoter methylation
VI To evaluate the impact of adding ipilimumab and nivolumab to radiotherapy versus adding temozolomide to radiotherapy on neurocognitive function NCF in patients with newly diagnosed GBM without MGMT promoter methylation
EXPLORATORY OBJECTIVES
I To explore biomarkers in pre-treatment archival tumor tissue that may predict efficacy of ipilimumab and nivolumab as measured by OS PFS and 2-year OS rate such as but not limited to
Ia PDL1 expression Ib Mutational burden II To explore in the two treatment separately whether the MGMT protein expression correlates with clinical outcomes including OS PFS and 2-year OS rate
III To evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms
OUTLINE Patients are randomized to 1 of 2 arms
ARM 1 Patients undergo radiation therapy for 5 days per week Monday-Friday for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide orally PO daily for 6 weeks After radiation patients may wear the Optune device at the discretion of the patient and their treating physician Beginning 1 month after radiation therapy patients receive temozolomide on days 1-5 Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity Patients also undergo contrast-enhanced brain magnetic resonance imaging MRI throughout the trial
ARM 2 Patients undergo radiation therapy for 5 days per week Monday-Friday for a total of 30 fractions over 6 weeks Starting on the first day of radiation patients also receive ipilimumab intravenously IV over 90 minutes once every 4 weeks Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression Patients also undergo contrast-enhanced brain MRI throughout the trial
After completion of study treatment patients are followed up every 3 months for year 1 then every 4 months for year 2 and then every 6 months thereafter
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA180868 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180868 |
| NCI-2020-03404 | REGISTRY | None | None |
| NRG-BN007 | OTHER | None | None |
| NRG-BN007 | OTHER | None | None |