Ignite Creation Date:
2025-12-25 @ 12:22 AM
Ignite Modification Date:
2026-01-07 @ 5:39 AM
Study NCT ID:
NCT03201458
Status:
COMPLETED
Last Update Posted:
2024-04-05
First Post:
2017-06-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Atezolizumab With or Without Cobimetinib in Treating Patients With Metastatic Bile Duct Cancer That Cannot Be Removed by Surgery or Gallbladder Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Randomized Phase 2 Study of Atezolizumab in Combination With Cobimetinib Versus Atezolizumab Monotherapy in Participants With Unresectable Cholangiocarcinoma
Status:
COMPLETED
Status Verified Date:
2024-02
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 randomized phase II trial studies how well atezolizumab with or without cobimetinib works in treating patients with bile duct cancer that has spread to other places in the body (metastatic) and cannot be removed by surgery (unresectable) or gallbladder cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving atezolizumab with cobimetinib may work better at treating patients with bile duct and gallbladder cancer.
Detailed Description:
PRIMARY OBJECTIVE:
I. To assess the progression free survival (PFS) of patients receiving atezolizumab monotherapy and cobimetinib in combination with atezolizumab for unresectable cholangiocarcinoma.
SECONDARY OBJECTIVES:
I. To assess the overall survival (OS) of patients receiving cobimetinib in combination with atezolizumab and atezolizumab monotherapy for unresectable cholangiocarcinoma.
II. To determine the objective response rate (ORR), defined as complete plus partial response, of cobimetinib in combination with atezolizumab and atezolizumab monotherapy in patients with unresectable cholangiocarcinoma.
III. To assess the safety and tolerability of cobimetinib in combination with atezolizumab and atezolizumab monotherapy in patients with unresectable cholangiocarcinoma.
IV. To determine the relationship between PD-L1 expression in tumor at baseline and on treatment, and response to treatment.
CORRELATIVE OBJECTIVES:
I. To determine the effect of cobimetinib on CD8+ T cell infiltration in tumor. II. To determine the effect of cobimetinib on T cell subpopulations systemically and in tumor, PD-1/PD-L1 expression on tumor, and MHC 1/2 expression.
III. To determine the effect of cobimetinib on markers of immune exhaustion and pro-apoptotic factors in CD8+ effector T cells.
IV. To explore the effect of cobimetinib on local and systemic immune activation pathways and immune suppressive pathways through expression profiling.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial and undergo tumor biopsy on study.
ARM B: Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 and cobimetinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial and undergo tumor biopsy on study.
After completion of study treatment, patients are followed up every 3 months until death, withdrawal of consent, or study closure, whichever occurs first.
I. To assess the progression free survival (PFS) of patients receiving atezolizumab monotherapy and cobimetinib in combination with atezolizumab for unresectable cholangiocarcinoma.
SECONDARY OBJECTIVES:
I. To assess the overall survival (OS) of patients receiving cobimetinib in combination with atezolizumab and atezolizumab monotherapy for unresectable cholangiocarcinoma.
II. To determine the objective response rate (ORR), defined as complete plus partial response, of cobimetinib in combination with atezolizumab and atezolizumab monotherapy in patients with unresectable cholangiocarcinoma.
III. To assess the safety and tolerability of cobimetinib in combination with atezolizumab and atezolizumab monotherapy in patients with unresectable cholangiocarcinoma.
IV. To determine the relationship between PD-L1 expression in tumor at baseline and on treatment, and response to treatment.
CORRELATIVE OBJECTIVES:
I. To determine the effect of cobimetinib on CD8+ T cell infiltration in tumor. II. To determine the effect of cobimetinib on T cell subpopulations systemically and in tumor, PD-1/PD-L1 expression on tumor, and MHC 1/2 expression.
III. To determine the effect of cobimetinib on markers of immune exhaustion and pro-apoptotic factors in CD8+ effector T cells.
IV. To explore the effect of cobimetinib on local and systemic immune activation pathways and immune suppressive pathways through expression profiling.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial and undergo tumor biopsy on study.
ARM B: Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 and cobimetinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial and undergo tumor biopsy on study.
After completion of study treatment, patients are followed up every 3 months until death, withdrawal of consent, or study closure, whichever occurs first.
Study Oversight
Has Oversight DMC:
False
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?: