Ignite Creation Date:
2024-05-06 @ 8:24 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06364410
Status:
RECRUITING
Last Update Posted:
2024-06-05
First Post:
2024-04-12
Brief Title:
Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan DS-8201a and Azenosertib ZN-c3 in Patients With Stomach or Other Solid Tumors
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 1 Study of Trastuzumab Deruxtecan DS-8201a in Combination With Azenosertib ZN-c3 in HER2-ExpressingAmplified Cyclin E-Amplified GastricGastroesophageal Junction Cancer and Other Solid Tumors With HER2 Expression
Status:
RECRUITING
Status Verified Date:
2024-10
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 I trial tests the safety side effects and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive and cyclin E amplified gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes locally advanced that have spread from where it first started primary site to other places in the body metastatic or that cannot be removed by surgery unresectable Azenosertib is in a class of medications called kinase inhibitors It inhibits a protein called Wee1 Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs leading to tumor cell death Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates It is composed of a monoclonal antibody called trastuzumab linked to a chemotherapy drug called deruxtecan Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them Giving azenosertib in combination with trastuzumab deruxtecan may be safe tolerable andor more effective in treating patients with locally advanced metastatic or unresectable HER2-positive gastric gastroesophageal junction or other solid tumors compared to just trastuzumab deruxtecan alone
Detailed Description:
PRIMARY OBJECTIVE
I To evaluate the safety and tolerability of trastuzumab deruxtecan T-DXd DS-8201a in combination with azenosertib ZN-c3 in human epidermal growth factor receptor 2 HER2-expressingamplified solid tumors
SECONDARY OBJECTIVES
I To observe and record the antitumor activity of the T-DXd DS-8201a and azenosertib ZN-c3 combination
II To assess the pharmacodynamic effects of T-DXd DS-8201a in combination with azenosertib ZN-c3
III To assess predictors of response and acquired resistance to the T-DXd DS-8201a and azenosertib ZN-c3 combination
OUTLINE This is a dose-escalation study of azenosertib followed by a dose-expansion study
DOSE ESCALATION Patients receive T-DXd intravenously IV over 30-90 minutes on day 1 of each cycle and azenosertib orally PO once daily QD on days 1-5 8-12 and 15-19 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo echocardiography ECHO or multigated acquisition scan MUGA and collection of blood samples at screening and on study and undergo computed tomography CT or magnetic resonance imaging MRI throughout the trial
DOSE EXPANSION Patients are assigned to 1 of 2 cohorts
COHORT 1 Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 8-12 and 15-19 of cycle 1 and days 1-5 8-12 and 15-19 in subsequent cycles Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial Patients also undergo biopsy at screening and on study
COHORT 2 Patients receive treatment as in the dose escalation arm Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial Patients also undergo biopsy at screening and on study
After completion of study treatment patients are followed up at 30 days and then every 3 months in years 1 and 2 and every 6 months in year 3
I To evaluate the safety and tolerability of trastuzumab deruxtecan T-DXd DS-8201a in combination with azenosertib ZN-c3 in human epidermal growth factor receptor 2 HER2-expressingamplified solid tumors
SECONDARY OBJECTIVES
I To observe and record the antitumor activity of the T-DXd DS-8201a and azenosertib ZN-c3 combination
II To assess the pharmacodynamic effects of T-DXd DS-8201a in combination with azenosertib ZN-c3
III To assess predictors of response and acquired resistance to the T-DXd DS-8201a and azenosertib ZN-c3 combination
OUTLINE This is a dose-escalation study of azenosertib followed by a dose-expansion study
DOSE ESCALATION Patients receive T-DXd intravenously IV over 30-90 minutes on day 1 of each cycle and azenosertib orally PO once daily QD on days 1-5 8-12 and 15-19 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo echocardiography ECHO or multigated acquisition scan MUGA and collection of blood samples at screening and on study and undergo computed tomography CT or magnetic resonance imaging MRI throughout the trial
DOSE EXPANSION Patients are assigned to 1 of 2 cohorts
COHORT 1 Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 8-12 and 15-19 of cycle 1 and days 1-5 8-12 and 15-19 in subsequent cycles Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial Patients also undergo biopsy at screening and on study
COHORT 2 Patients receive treatment as in the dose escalation arm Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial Patients also undergo biopsy at screening and on study
After completion of study treatment patients are followed up at 30 days and then every 3 months in years 1 and 2 and every 6 months in year 3
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 |
|---|---|---|---|
| UM1CA186688 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186688 |
| NCI-2024-02982 | REGISTRY | None | None |
| 10554 | OTHER | None | None |
| 10554 | OTHER | None | None |