Ignite Creation Date:
2024-05-06 @ 3:03 PM
Last Modification Date:
2024-10-26 @ 1:42 PM
Study NCT ID:
NCT04514497
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2020-08-14
Brief Title:
Testing the Addition of an Anti-cancer Drug BAY 1895344 to Usual Chemotherapy for Advanced Stage Solid Tumors With a Specific Focus on Patients With Small Cell Lung Cancer Poorly Differentiated Neuroendocrine Cancer and Pancreatic Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
BAY 1895344 Plus Topoisomerase-1 Top1 Inhibitors in Patients With Advanced Solid Tumors Phase I Studies With Expansion Cohorts in Small Cell Lung Carcinoma SCLC Poorly Differentiated Neuroendocrine Carcinoma PD-NEC and Pancreatic Adenocarcinoma PDA
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 I trial tests the safety side effects and best dose of BAY 1895344 when given together with usual chemotherapy irinotecan or topotecan in treating patients with solid tumors that may have spread from where it first started to nearby tissue lymph nodes or distant parts of the body advanced with a specific focus on small cell lung cancer poorly differentiated neuroendocrine cancer and pancreatic cancer BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Chemotherapy drugs such as irinotecan and topotecan 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 Adding BAY 1895344 to irinotecan or topotecan may be safe and tolerable in treating patients with advanced solid tumors
Detailed Description:
PRIMARY OBJECTIVES
I To assess safety and tolerability of each of the elimusertib BAY 1895344 plus topoisomerase 1 top1 inhibitor irinotecan hydrochloride irinotecan or topotecan hydrochloride topotecan combinations
II To estimate maximum tolerated dose MTD and recommended phase 2 dose RP2D of each of the combinations
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To estimate objective response rate ORR progression free survival PFS overall survival OS and duration of response DOR in patients treated with each combination
III To estimate plasma pharmacokinetic PK characteristics of BAY 1895344 plus each top1 inhibitor irinotecan or topotecan when used in combination
IV To estimate changes in pharmacodynamic PD markers of deoxyribonucleic acid DNA damage gamma-H2AX phosphorylated pS343-NBS1 elicited by each combination from on-treatment tumor biopsies in dose expansion cohorts only
EXPLORATORY OBJECTIVES
I To estimate response outcomes ORR PFS OS DOR in study patients by tumor ataxia telangiectasia mutated ATM expression loss assessed by immunohistochemistry IHC
II To estimate response outcomes ORR PFS OS DOR in study patients with tumor DNA damage response DDR mutations assessed by whole exome sequencing WES ribonucleic acid RNA sequencing RNA Seq and circulating tumor DNA ctDNA analysis
OUTLINE This is a dose-escalation study Patients are assigned to 1 of 3 cohorts
COHORT I Patients receive elimusertib orally PO twice daily BID on days 1 and 2 and irinotecan intravenously IV over 90 minutes on day 1 of each cycle Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity Patients undergo computed tomography CT andor magnetic resonance imaging MRI throughout the study tumor biopsy at screening and on study and collection of blood samples at screening
COHORT II Patients receive elimusertib PO once daily QD on days 2 3 9 10 16 and 17 of cycle 1 and 2 and on days 2 3 9 and 10 of each cycle thereafter Patients receive irinotecan IV over 90 minutes on days 1 8 and 15 of cycle 1 and 2 and on days 1 and 8 of each cycle thereafter Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients undergo CT andor MRI throughout the study tumor biopsy at screening and on study and collection of blood samples at screening
COHORT III Patients receive elimusertib PO QD on days 2 and 5 and topotecan IV over 30 minutes on days 1-5 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients undergo CT andor MRI throughout the study tumor biopsy at screening and on study and collection of blood samples at screening
After completion of study treatment patients are followed every 2 months for up to 6 months
I To assess safety and tolerability of each of the elimusertib BAY 1895344 plus topoisomerase 1 top1 inhibitor irinotecan hydrochloride irinotecan or topotecan hydrochloride topotecan combinations
II To estimate maximum tolerated dose MTD and recommended phase 2 dose RP2D of each of the combinations
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To estimate objective response rate ORR progression free survival PFS overall survival OS and duration of response DOR in patients treated with each combination
III To estimate plasma pharmacokinetic PK characteristics of BAY 1895344 plus each top1 inhibitor irinotecan or topotecan when used in combination
IV To estimate changes in pharmacodynamic PD markers of deoxyribonucleic acid DNA damage gamma-H2AX phosphorylated pS343-NBS1 elicited by each combination from on-treatment tumor biopsies in dose expansion cohorts only
EXPLORATORY OBJECTIVES
I To estimate response outcomes ORR PFS OS DOR in study patients by tumor ataxia telangiectasia mutated ATM expression loss assessed by immunohistochemistry IHC
II To estimate response outcomes ORR PFS OS DOR in study patients with tumor DNA damage response DDR mutations assessed by whole exome sequencing WES ribonucleic acid RNA sequencing RNA Seq and circulating tumor DNA ctDNA analysis
OUTLINE This is a dose-escalation study Patients are assigned to 1 of 3 cohorts
COHORT I Patients receive elimusertib orally PO twice daily BID on days 1 and 2 and irinotecan intravenously IV over 90 minutes on day 1 of each cycle Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity Patients undergo computed tomography CT andor magnetic resonance imaging MRI throughout the study tumor biopsy at screening and on study and collection of blood samples at screening
COHORT II Patients receive elimusertib PO once daily QD on days 2 3 9 10 16 and 17 of cycle 1 and 2 and on days 2 3 9 and 10 of each cycle thereafter Patients receive irinotecan IV over 90 minutes on days 1 8 and 15 of cycle 1 and 2 and on days 1 and 8 of each cycle thereafter Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients undergo CT andor MRI throughout the study tumor biopsy at screening and on study and collection of blood samples at screening
COHORT III Patients receive elimusertib PO QD on days 2 and 5 and topotecan IV over 30 minutes on days 1-5 of each cycle Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity Patients undergo CT andor MRI throughout the study tumor biopsy at screening and on study and collection of blood samples at screening
After completion of study treatment patients are followed every 2 months for up to 6 months
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 |
|---|---|---|---|
| UM1CA186689 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186689 |
| NCI-2020-05958 | REGISTRY | None | None |
| 10402 | OTHER | None | None |
| 10402 | OTHER | None | None |