Ignite Creation Date:
2024-05-06 @ 7:17 PM
Last Modification Date:
2024-10-26 @ 3:03 PM
Study NCT ID:
NCT05950464
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2023-07-15
Brief Title:
Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1B Study of Combination ATR M1774 and BET Inhibition ZEN00-3694 to Exploit ARID1A Loss in Recurrent Ovarian and Endometrial Cancer
Status:
RECRUITING
Status Verified Date:
2024-08
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 Ib trial tests the safety side effects and best dose of M1774 when given with ZEN-3694 in treating patients with ovarian and endometrial cancer that has come back recurrent M1774 and ZEN-3694 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth M1774 and ZEN-3694 combined together has demonstrated to be better than either drug alone in killing ovarian tumor cells
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD and the dose-limiting toxicities DLTs for combination of tuvusertib ATR inhibitor M1774 and BET bromodomain inhibitor ZEN-3694 BET inhibitor ZEN003694 in women with recurrent clear cell endometrioid and platinum resistant high grade serous ovarian carcinoma HGSOC and clear cell and endometrioid endometrial carcinoma irrespective of ARID1A status PART I
II To determine safety and tolerability in ARID1A pathogenic alteration ARID1AMUTATION MUT and ARID1A wildtype ARID1AWT cohorts ARID1A is an integral biomarker in an expansion phase PART II
III To determine change in pharmacodynamic biomarker expression of gammaH2AX for ATR inhibition integral biomarker from pre-treatment and on-treatment tumor samples in ARID1AMUT and ARID1AWT expansion cohorts by immunohistochemistry IHC PART II
SECONDARY OBJECTIVES
I To evaluate change in pharmacodynamic biomarker expression of cmyc for BET inhibition integrated biomarker from pre-treatment and on-treatment tumor samples in ARID1AMUT and ARID1AWT expansion cohorts by Digital Spatial Profiling DSP PART II
II To evaluate change in pharmacodynamic biomarker expression of gammaH2AX for ATR inhibition integrated biomarker from pre-treatment and on-treatment tumor samples in ARID1AMUT and ARID1AWT expansion cohorts by DSP PART II
III To investigate if ARID1A protein by IHC and DSP correlates with ARID1A pathogenic alteration in pre-treatment tumor biopsy samples PART II
IV To estimate objective response rate ORR and progression free survival PFS at 6 months in ARID1A pathogenic alteration and wildtype cohorts PART II
EXPLORATORY OBJECTIVES
I To evaluate the pharmacokinetics of ZEN003694 and its active metabolite ZEN003791 when the drug is taken alone and in combination with M1774 as well as M1774 pharmacokinetics in the combination PART I
II To assess if ARID1A pathogenic alteration status by Next Generation Sequencing NGS correlates with ARID1A protein by IHC utilizing existing archival tissue and evaluate retrospectively PART I
III To evaluate objective response rate ORR and progression free survival PFS at 6 months and to evaluate if these correlate with ARID1A pathogenic alteration status by Next Generation Sequencing NGS and with ARID1A protein by IHC PART I
IV In patients with prior somatic tumor testing by Next Generation Sequencing will obtain results and correlate molecular profiles ie ARID1A pathogenic alteration PIK3CA pathogenic alteration C-myc amplification ATM pathogenic alteration with response by Response Evaluation Criteria in Solid Tumors RECIST 11 or CA-125 by Gynecological Cancer Intergroup GCIG Rustin et al 2011 PART I
V To evaluate the pharmacokinetics of ZEN003694 and its active metabolite ZEN003791 when the drug is taken alone and in combination with M1774 as well as M1774 pharmacokinetics in the combination PART II
VI To assess if there is a greater overall response by RECIST 11 and CA-125 by GCIG Rustin et al 2011 in ARID1A pathogenic alteration cohort ARID1AMUT compared to ARID1A wildtype ARID1AWT cohort PART II
VII To correlate pharmacodynamics and pharmacokinetics in ARID1AMUT and ARID1AWT expansion cohorts at the MTD determine if drug levels affect drug target engagement and expression eg gamma gH2AX and MYC PART II
VIII To estimate overall survival OS in ARID1A pathogenic alteration versus vs wildtype cohorts PART II
IX To identify biomarkers of response we will correlate ORR and PFS with ARID1A gene alteration ARID1A protein level IHC and DSP gammaH2AX IHC and DSP C-myc DSP and total tot ATM DSP and HEXIM1 by ribonucleic acid RNA sequencing Seq in tumor biopsies PART II
X To explore if liquid biopsies are a good surrogate for tumor ARID1A pathogenic alteration PART II
XI To evaluate if ARID1A expression changes over time we will compare ARID1A expression by NGS gene alteration and IHC protein using existing archival tumor to most recent pre-treatment biopsy samples required for PART II expansion cohort PART II
OUTLINE This is a dose-escalation study of tuvusertib followed by a dose-expansion study
Patients receive tuvusertib and BET bromodomain inhibitor ZEN-3694 orally PO on study Patients in the dose-escalation phase of the trial also undergo electrocardiography ECG during screening collection of blood samples on study and x-ray computed tomography CT or magnetic resonance imaging MRI throughout the trial Patients in the dose-expansion phase of the trial also undergo ECG during screening biopsies during screening and on study and x-ray CT or MRI and collection of blood samples throughout the trial
After study completion patients are followed every 3 months for 2 years and then every 6 months for 3 years or until the study is terminated
I To determine the maximum tolerated dose MTD and the dose-limiting toxicities DLTs for combination of tuvusertib ATR inhibitor M1774 and BET bromodomain inhibitor ZEN-3694 BET inhibitor ZEN003694 in women with recurrent clear cell endometrioid and platinum resistant high grade serous ovarian carcinoma HGSOC and clear cell and endometrioid endometrial carcinoma irrespective of ARID1A status PART I
II To determine safety and tolerability in ARID1A pathogenic alteration ARID1AMUTATION MUT and ARID1A wildtype ARID1AWT cohorts ARID1A is an integral biomarker in an expansion phase PART II
III To determine change in pharmacodynamic biomarker expression of gammaH2AX for ATR inhibition integral biomarker from pre-treatment and on-treatment tumor samples in ARID1AMUT and ARID1AWT expansion cohorts by immunohistochemistry IHC PART II
SECONDARY OBJECTIVES
I To evaluate change in pharmacodynamic biomarker expression of cmyc for BET inhibition integrated biomarker from pre-treatment and on-treatment tumor samples in ARID1AMUT and ARID1AWT expansion cohorts by Digital Spatial Profiling DSP PART II
II To evaluate change in pharmacodynamic biomarker expression of gammaH2AX for ATR inhibition integrated biomarker from pre-treatment and on-treatment tumor samples in ARID1AMUT and ARID1AWT expansion cohorts by DSP PART II
III To investigate if ARID1A protein by IHC and DSP correlates with ARID1A pathogenic alteration in pre-treatment tumor biopsy samples PART II
IV To estimate objective response rate ORR and progression free survival PFS at 6 months in ARID1A pathogenic alteration and wildtype cohorts PART II
EXPLORATORY OBJECTIVES
I To evaluate the pharmacokinetics of ZEN003694 and its active metabolite ZEN003791 when the drug is taken alone and in combination with M1774 as well as M1774 pharmacokinetics in the combination PART I
II To assess if ARID1A pathogenic alteration status by Next Generation Sequencing NGS correlates with ARID1A protein by IHC utilizing existing archival tissue and evaluate retrospectively PART I
III To evaluate objective response rate ORR and progression free survival PFS at 6 months and to evaluate if these correlate with ARID1A pathogenic alteration status by Next Generation Sequencing NGS and with ARID1A protein by IHC PART I
IV In patients with prior somatic tumor testing by Next Generation Sequencing will obtain results and correlate molecular profiles ie ARID1A pathogenic alteration PIK3CA pathogenic alteration C-myc amplification ATM pathogenic alteration with response by Response Evaluation Criteria in Solid Tumors RECIST 11 or CA-125 by Gynecological Cancer Intergroup GCIG Rustin et al 2011 PART I
V To evaluate the pharmacokinetics of ZEN003694 and its active metabolite ZEN003791 when the drug is taken alone and in combination with M1774 as well as M1774 pharmacokinetics in the combination PART II
VI To assess if there is a greater overall response by RECIST 11 and CA-125 by GCIG Rustin et al 2011 in ARID1A pathogenic alteration cohort ARID1AMUT compared to ARID1A wildtype ARID1AWT cohort PART II
VII To correlate pharmacodynamics and pharmacokinetics in ARID1AMUT and ARID1AWT expansion cohorts at the MTD determine if drug levels affect drug target engagement and expression eg gamma gH2AX and MYC PART II
VIII To estimate overall survival OS in ARID1A pathogenic alteration versus vs wildtype cohorts PART II
IX To identify biomarkers of response we will correlate ORR and PFS with ARID1A gene alteration ARID1A protein level IHC and DSP gammaH2AX IHC and DSP C-myc DSP and total tot ATM DSP and HEXIM1 by ribonucleic acid RNA sequencing Seq in tumor biopsies PART II
X To explore if liquid biopsies are a good surrogate for tumor ARID1A pathogenic alteration PART II
XI To evaluate if ARID1A expression changes over time we will compare ARID1A expression by NGS gene alteration and IHC protein using existing archival tumor to most recent pre-treatment biopsy samples required for PART II expansion cohort PART II
OUTLINE This is a dose-escalation study of tuvusertib followed by a dose-expansion study
Patients receive tuvusertib and BET bromodomain inhibitor ZEN-3694 orally PO on study Patients in the dose-escalation phase of the trial also undergo electrocardiography ECG during screening collection of blood samples on study and x-ray computed tomography CT or magnetic resonance imaging MRI throughout the trial Patients in the dose-expansion phase of the trial also undergo ECG during screening biopsies during screening and on study and x-ray CT or MRI and collection of blood samples throughout the trial
After study completion patients are followed every 3 months for 2 years and then every 6 months for 3 years or until the study is terminated
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 |
|---|---|---|---|
| U10CA180868 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180868 |
| NCI-2023-03408 | REGISTRY | None | None |
| NRG-GY031 | OTHER | None | None |
| NRG-GY031 | OTHER | None | None |