Ignite Creation Date:
2024-05-06 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 12:48 PM
Study NCT ID:
NCT03566485
Status:
TERMINATED
Last Update Posted:
2021-08-11
First Post:
2018-06-11
Brief Title:
Atezolizumab and Cobimetinib or Idasanutlin in Participants With Stage IV or Unresectable Recurrent Estrogen Receptor Positive Breast Cancer
Sponsor:
Vanderbilt-Ingram Cancer Center
Organization:
Vanderbilt-Ingram Cancer Center
Study Overview
Official Title:
BRE 17107 A Phase IbII Trial of Atezolizumab an Anti-PD-L1 Monoclonal Antibody With Cobimetinib a MEK12 Inhibitor or Idasanutlin an MDM2 Antagonist in Metastatic ER Breast Cancer
Status:
TERMINATED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Low accrualLoss of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies the side effects and best dose of idasanutlin when given together with atezolizumab and to see how well atezolizumab and cobimetinib or idasanutlin work in treating participants with stage IV estrogen-receptor positive ER breast cancer or ER breast cancer that has come back recurrent and cannot be removed by surgery unresectable Monoclonal antibodies such as atezolizumab may interfere with the ability of tumor cells to grow and spread Cobimetinib and idasanutlin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Giving atezolizumab with cobimetinib or atezolizumab with idasanutlin may work better in treating participants with estrogen-receptor positive breast cancer
Detailed Description:
PRIMARY OBJECTIVES
I To determine the safety and tolerability of atezolizumab and idasanutlin in patients with estrogen receptor positive ER metastatic breast cancer mBC Phase I
II To determine the anti-tumor effect of atezolizumab and cobimetinib or idasanutlin in patients with ER mBC Phase II
SECONDARY OBJECTIVES
I To determine the anti-tumor duration of effect of atezolizumab and cobimetinib or idasanutlin in patients with ER mBC Phase II
II To determine the safety and tolerability of atezolizumab and cobimetinib or idasanutlin in patients with ER mBC Phase II
EXPLORATORY OBJECTIVES
I To evaluate if CD8 T cells are enhanced in the tumor with either MEK or MDM2 inhibition Phase II
II To evaluate if MHC-III andor PD-L1 expression is enhanced with MEK inhibition Phase II
III To evaluate if T cell chemotractants CCL5 CXCL9101113 are upregulated upon MDM2 antagonism Phase II
IV To determine if baseline or changes in PDL1 expression MHC expression presence of tumor infiltrating lymphocytes neoantigen expression mutation burden using ribonucleic acid RNA-and whole exome sequencing CCL5 CXCL9 CXCL10 CXCL11 and CXCL13 correlate with clinical outcome Phase II
V To determine if immunological activity of MEK inhibition can be tracked noninvasively using Zr89-atezolizumab Phase II
OUTLINE This is a phase 1 dose-escalation study of idasanutlin followed by a phase II study Participants are assigned to 1 of 2 arms
ARM I Participants with TP53 gene mutation receive atezolizumab intravenously IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses and cobimetinib orally PO daily on days 1-21 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
ARM II Participants without TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses and idasanutlin PO daily on days 1-5 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment participants are followed for 28 days
I To determine the safety and tolerability of atezolizumab and idasanutlin in patients with estrogen receptor positive ER metastatic breast cancer mBC Phase I
II To determine the anti-tumor effect of atezolizumab and cobimetinib or idasanutlin in patients with ER mBC Phase II
SECONDARY OBJECTIVES
I To determine the anti-tumor duration of effect of atezolizumab and cobimetinib or idasanutlin in patients with ER mBC Phase II
II To determine the safety and tolerability of atezolizumab and cobimetinib or idasanutlin in patients with ER mBC Phase II
EXPLORATORY OBJECTIVES
I To evaluate if CD8 T cells are enhanced in the tumor with either MEK or MDM2 inhibition Phase II
II To evaluate if MHC-III andor PD-L1 expression is enhanced with MEK inhibition Phase II
III To evaluate if T cell chemotractants CCL5 CXCL9101113 are upregulated upon MDM2 antagonism Phase II
IV To determine if baseline or changes in PDL1 expression MHC expression presence of tumor infiltrating lymphocytes neoantigen expression mutation burden using ribonucleic acid RNA-and whole exome sequencing CCL5 CXCL9 CXCL10 CXCL11 and CXCL13 correlate with clinical outcome Phase II
V To determine if immunological activity of MEK inhibition can be tracked noninvasively using Zr89-atezolizumab Phase II
OUTLINE This is a phase 1 dose-escalation study of idasanutlin followed by a phase II study Participants are assigned to 1 of 2 arms
ARM I Participants with TP53 gene mutation receive atezolizumab intravenously IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses and cobimetinib orally PO daily on days 1-21 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
ARM II Participants without TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses and idasanutlin PO daily on days 1-5 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
After completion of study treatment participants are followed for 28 days
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 |
|---|---|---|---|
| NCI-2018-01159 | REGISTRY | NCI Clinical Trials Reporting Program | None |