Ignite Creation Date:
2024-05-06 @ 6:32 PM
Last Modification Date:
2024-10-26 @ 2:49 PM
Study NCT ID:
NCT05691504
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2023-01-18
Brief Title:
Testing the Combination of APG-1252 Pelcitoclax and Cobimetinib in Recurrent Ovarian and Endometrial Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1 Study of APG-1252 Pelcitoclax and Cobimetinib in Recurrent Ovarian and Endometrial Cancers
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety side effects and best dose of combination therapy with pelcitoclax APG-1252 and cobimetinib in treating patients with ovarian and endometrial cancers that have come back after a period of improvement recurrent APG-1252 is a drug that inhibits activity of proteins that prevent cell death leading to increased cell death and reduced cell growth 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 APG-1252 in combination with cobimetinib may shrink or stabilize tumor in patients with recurrent ovarian and endometrial cancers
Detailed Description:
PRIMARY OBJECTIVE
I To establish the recommended phase 2 dosing RP2D for combination pelcitoclax APG-1252 and cobimetinib in advancedrecurrent endometrial and ovarian cancers
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To assess the side effects associated with combination APG-1252 and cobimetinib in advancedrecurrent endometrial and ovarian cancers as measured by treatment-emergent and treatment-related adverse events by Common Terminology Criteria for Adverse Events CTCAE criteria
III To assess the activity of combination APG-1252 and cobimetinib in advancedrecurrent endometrial and ovarian cancers via measures of clinical activity including response rate RR progression-free survival PFS clinical benefit rate CBR and duration of response DoR
TRANSLATIONAL OBJECTIVES
I To evaluate the pharmacodynamic effects of combination APG-1252 and cobimetinib on BCL-xL activity including BCL-xLBAX and BCL-xL-BAK heterodimers as measured by the National Clinical Laboratory Network NCLN apoptosis multiplex immunoassay
II To evaluate markers of response and resistance to APG-1252 and cobimetinib via whole exome sequencing and ribonucleic acid RNA sequencing obtained in pre-treatmentarchival and on-treatment samples
III To explore the effect of combination APG-1252 and cobimetinib on RAS pathway signaling as measured by the NCLN ERKMEK multiple immunoassay and the association between RAS pathway activation with activity of combination APG-1252 and cobimetinib
IV To explore markers of response and resistance to APG-1252 and cobimetinib through evaluation of BIM and MCL1 expression and RAS pathway signaling by reverse phase protein array RPPA and by BIM and pERK expression by immunohistochemistry
V To determine pharmacokinetic PK parameters of APG-1252 and cobimetinib in combination
VI To investigate RAS allelic burden and resistance mutations in patients receiving combination APG-1252 and cobimetinib
OUTLINE This is a dose-escalation study of APG-1252 and cobimetinib followed by a dose-expansion study
Patients receive APG-1252 intravenously IV once a week Q7D Patients also receive cobimetinib orally PO once a day QD on days 1-21 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients also undergo biopsy and collection of blood on study and undergo computed tomography CT andor magnetic resonance MRI throughout the trial Patients undergo echocardiography ECHO or multigated acquisition scan MUGA during screening and on study
Patients are followed for up to 30 days after removal from study therapy
I To establish the recommended phase 2 dosing RP2D for combination pelcitoclax APG-1252 and cobimetinib in advancedrecurrent endometrial and ovarian cancers
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To assess the side effects associated with combination APG-1252 and cobimetinib in advancedrecurrent endometrial and ovarian cancers as measured by treatment-emergent and treatment-related adverse events by Common Terminology Criteria for Adverse Events CTCAE criteria
III To assess the activity of combination APG-1252 and cobimetinib in advancedrecurrent endometrial and ovarian cancers via measures of clinical activity including response rate RR progression-free survival PFS clinical benefit rate CBR and duration of response DoR
TRANSLATIONAL OBJECTIVES
I To evaluate the pharmacodynamic effects of combination APG-1252 and cobimetinib on BCL-xL activity including BCL-xLBAX and BCL-xL-BAK heterodimers as measured by the National Clinical Laboratory Network NCLN apoptosis multiplex immunoassay
II To evaluate markers of response and resistance to APG-1252 and cobimetinib via whole exome sequencing and ribonucleic acid RNA sequencing obtained in pre-treatmentarchival and on-treatment samples
III To explore the effect of combination APG-1252 and cobimetinib on RAS pathway signaling as measured by the NCLN ERKMEK multiple immunoassay and the association between RAS pathway activation with activity of combination APG-1252 and cobimetinib
IV To explore markers of response and resistance to APG-1252 and cobimetinib through evaluation of BIM and MCL1 expression and RAS pathway signaling by reverse phase protein array RPPA and by BIM and pERK expression by immunohistochemistry
V To determine pharmacokinetic PK parameters of APG-1252 and cobimetinib in combination
VI To investigate RAS allelic burden and resistance mutations in patients receiving combination APG-1252 and cobimetinib
OUTLINE This is a dose-escalation study of APG-1252 and cobimetinib followed by a dose-expansion study
Patients receive APG-1252 intravenously IV once a week Q7D Patients also receive cobimetinib orally PO once a day QD on days 1-21 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients also undergo biopsy and collection of blood on study and undergo computed tomography CT andor magnetic resonance MRI throughout the trial Patients undergo echocardiography ECHO or multigated acquisition scan MUGA during screening and on study
Patients are followed for up to 30 days after removal from study therapy
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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2022-11033 | REGISTRY | None | None |
| 10597 | OTHER | None | None |
| 10597 | OTHER | None | None |
| UM1CA186709 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186709 |