Ignite Creation Date:
2024-05-06 @ 3:07 AM
Last Modification Date:
2024-10-26 @ 11:28 AM
Study NCT ID:
NCT02203513
Status:
TERMINATED
Last Update Posted:
2022-09-10
First Post:
2014-07-29
Brief Title:
A Phase II Single Arm Pilot Study of the Chk12 Inhibitor LY2606368 in BRCA12 Mutation Associated Breast or Ovarian Cancer Triple Negative Breast Cancer High Grade Serous Ovarian Cancer and Metastatic Castrate-Resistant Prostate Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Single Arm Pilot Study of the Chk12 Inhibitor LY2606368 In BRCA12 Mutation Associated Breast or Ovarian Cancer Triple Negative Breast Cancer and High Grade Serous Ovarian Cancer
Status:
TERMINATED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Eli Lilly prematurely terminated the study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
All cells go through cycles which allow them to divide In normal cells checkpoint kinase 1 Chk1 and checkpoint kinase 2 Chk2 CHEK 2 Chk12 stop cell division at various points to allow any damage to deoxyribonucleic acid DNA to be repaired
When Chk12 are not present cells stop dividing and eventually die Chk12 Inhibitor Prexasertib LY2606368 blocks the Chk12 proteins
Researchers hope that by blocking Chk12 it will cause tumor cells to die thereby shrinking tumors
Objective
- To see if LY2606368 helps shrink tumors in patients with certain breast ovarian or prostate cancers
Eligibility
- Participants at least 18 years old with breast or ovarian cancer They must have a mutation in BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2 BRCA12 genes for group 1 high grade serious ovarian cancer without BRCA12 mutation for group 2 or triple negative breast cancer without BRCA12 mutation for group 3 or prostate cancer with or without BRCA12 mutation for group 4
Design
Participants will be screened with a medical history and physical exam They will have blood tests an electrocardiogram ECG heart test scans and X-rays They will have a piece of their tumor removed at entry computed tomography CT-assisted biopsy
Study Day 1 Participants will have a physical exam and blood drawn They may have a CT scan of the chest abdomen and pelvis
Day 1 and Day 15 of each 28-day cycle Participants will receive the study drug through an intravenous IV
Vital signs will be checked before and after An ECG will be done within 1 hour after
Day 15 and Day 28 Participants will have a physical exam blood drawn and a 12 lead ECG
Cycle 1 Participants will have weekly phone calls and blood draws Participants may have another CT-assisted biopsy at the end of cycle 1
Cycle 2 and beyond blood will be drawn every other week for routine blood tests
Participants will have an after-study visit with a physical exam and blood tests Participants may have another biopsy when they progressed on treatment They will have scans of the chest pelvis and abdomen and a 12 lead ECG
All cells go through cycles which allow them to divide In normal cells checkpoint kinase 1 Chk1 and checkpoint kinase 2 Chk2 CHEK 2 Chk12 stop cell division at various points to allow any damage to deoxyribonucleic acid DNA to be repaired
When Chk12 are not present cells stop dividing and eventually die Chk12 Inhibitor Prexasertib LY2606368 blocks the Chk12 proteins
Researchers hope that by blocking Chk12 it will cause tumor cells to die thereby shrinking tumors
Objective
- To see if LY2606368 helps shrink tumors in patients with certain breast ovarian or prostate cancers
Eligibility
- Participants at least 18 years old with breast or ovarian cancer They must have a mutation in BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2 BRCA12 genes for group 1 high grade serious ovarian cancer without BRCA12 mutation for group 2 or triple negative breast cancer without BRCA12 mutation for group 3 or prostate cancer with or without BRCA12 mutation for group 4
Design
Participants will be screened with a medical history and physical exam They will have blood tests an electrocardiogram ECG heart test scans and X-rays They will have a piece of their tumor removed at entry computed tomography CT-assisted biopsy
Study Day 1 Participants will have a physical exam and blood drawn They may have a CT scan of the chest abdomen and pelvis
Day 1 and Day 15 of each 28-day cycle Participants will receive the study drug through an intravenous IV
Vital signs will be checked before and after An ECG will be done within 1 hour after
Day 15 and Day 28 Participants will have a physical exam blood drawn and a 12 lead ECG
Cycle 1 Participants will have weekly phone calls and blood draws Participants may have another CT-assisted biopsy at the end of cycle 1
Cycle 2 and beyond blood will be drawn every other week for routine blood tests
Participants will have an after-study visit with a physical exam and blood tests Participants may have another biopsy when they progressed on treatment They will have scans of the chest pelvis and abdomen and a 12 lead ECG
Detailed Description:
Background
Checkpoint kinases 1 and 2 Chk12 are major regulators of the cell cycle and are intimately associated with the cellular response to deoxyribonucleic acid DNA damage and repair Chk12 also function as the primary mediators of cell cycle arrest in tumors with tumor protein P53 p53 dysfunction such as high-grade serous ovarian cancer HGSOC and triple negative breast cancer TNBC
Participants with germline BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2 BRCA12 mutation have inherent defects in DNA damage repair pathways
Chk12 inhibition alone yielded DNA damage and mitotic catastrophe preclinically even in the absence of DNA damage by external agents in tumors with underlying DNA repair dysfunction
The second-generation Chk12 inhibitor Prexasertib LY2606368 yielded safety and preliminary single agent activity in advanced cancer participants
We hypothesize that LY2606368 will result in clinical benefit in participants with Germline BRCA-Mutated gBRCAm-associated breast or ovarian cancers and HGSOC and TNBC with low genetic risk
Objectives
To determine the objective response rate Complete Response CRPartial Response PR of single agent LY2606368 in patients with gBRCAm-associated breast or ovarian cancer HGSOC and TNBC with low genetic risk
To determine the safety and toxicity and progression-free interval PFI of LY2606368 in pretreated participants
To determine biochemical changes in the DNA damage repair and cell cycle check point pathways in tumor and blood samples in response to treatment
To determine potential resistance mechanisms to LY2606368 treatment in HGSOC
Eligibility
Participants with recurrentrefractory BReast CAncer gene BRCA mutant breast or ovarian cancer HGSOC and TNBC for whom there remains no standard curative measures
A documented deleterious germline or somatic BRCA mutation for breast or ovarian cancer participants enrolling in Cohort 1
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for HGSOC Cohort 2
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for TNBC Cohort 3
Effective with amendment I version date 4242017 Metastatic Castration-Resistant Prostate Cancer mCRPC Cohort 4 was closed
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable and biopsiable disease Cohort 5
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable but without biopsiable disease Cohort 6
Participants must be off prior chemotherapy radiation therapy hormonal therapy or biological therapy for at least 4 weeks
Eastern Cooperative Oncology Group ECOG performance status 0-2 and adequate organ and marrow function
Design
This is an open label single arm phase II trial to examine activity of LY2606368 in participants in the 6 independent cohorts Cohorts 1-6
LY2606368 will be dosed at the recommended phase 2 dose RP2D of 105 mgm2 intravenous IV once every 14 days of a 28 day-cycle
Research samples including whole blood circulating tumor cells CTCs and tumor biopsies will be obtained for pharmacodynamics PD endpoints at baseline Cycle 1 Day 15 6-24hour hr post-2nd dose andor at progression in all participants Tumor biopsies will not be performed in Cohort 6
Participants Cohorts 1-3 5 and 6 will be evaluated every two cycles for response using Response Evaluation Criteria in Solid Tumors RECIST v11 and every cycle for safety using Common Terminology Criteria for Adverse Events CTCAE v40
Checkpoint kinases 1 and 2 Chk12 are major regulators of the cell cycle and are intimately associated with the cellular response to deoxyribonucleic acid DNA damage and repair Chk12 also function as the primary mediators of cell cycle arrest in tumors with tumor protein P53 p53 dysfunction such as high-grade serous ovarian cancer HGSOC and triple negative breast cancer TNBC
Participants with germline BRCA1 BReast CAncer gene 1 and BRCA2 BReast CAncer gene 2 BRCA12 mutation have inherent defects in DNA damage repair pathways
Chk12 inhibition alone yielded DNA damage and mitotic catastrophe preclinically even in the absence of DNA damage by external agents in tumors with underlying DNA repair dysfunction
The second-generation Chk12 inhibitor Prexasertib LY2606368 yielded safety and preliminary single agent activity in advanced cancer participants
We hypothesize that LY2606368 will result in clinical benefit in participants with Germline BRCA-Mutated gBRCAm-associated breast or ovarian cancers and HGSOC and TNBC with low genetic risk
Objectives
To determine the objective response rate Complete Response CRPartial Response PR of single agent LY2606368 in patients with gBRCAm-associated breast or ovarian cancer HGSOC and TNBC with low genetic risk
To determine the safety and toxicity and progression-free interval PFI of LY2606368 in pretreated participants
To determine biochemical changes in the DNA damage repair and cell cycle check point pathways in tumor and blood samples in response to treatment
To determine potential resistance mechanisms to LY2606368 treatment in HGSOC
Eligibility
Participants with recurrentrefractory BReast CAncer gene BRCA mutant breast or ovarian cancer HGSOC and TNBC for whom there remains no standard curative measures
A documented deleterious germline or somatic BRCA mutation for breast or ovarian cancer participants enrolling in Cohort 1
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for HGSOC Cohort 2
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for TNBC Cohort 3
Effective with amendment I version date 4242017 Metastatic Castration-Resistant Prostate Cancer mCRPC Cohort 4 was closed
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable and biopsiable disease Cohort 5
Negative BRCA mutation testing or negative family history of hereditary breast and ovarian cancer syndrome for recurrent platinum-resistant HGSOC with measurable but without biopsiable disease Cohort 6
Participants must be off prior chemotherapy radiation therapy hormonal therapy or biological therapy for at least 4 weeks
Eastern Cooperative Oncology Group ECOG performance status 0-2 and adequate organ and marrow function
Design
This is an open label single arm phase II trial to examine activity of LY2606368 in participants in the 6 independent cohorts Cohorts 1-6
LY2606368 will be dosed at the recommended phase 2 dose RP2D of 105 mgm2 intravenous IV once every 14 days of a 28 day-cycle
Research samples including whole blood circulating tumor cells CTCs and tumor biopsies will be obtained for pharmacodynamics PD endpoints at baseline Cycle 1 Day 15 6-24hour hr post-2nd dose andor at progression in all participants Tumor biopsies will not be performed in Cohort 6
Participants Cohorts 1-3 5 and 6 will be evaluated every two cycles for response using Response Evaluation Criteria in Solid Tumors RECIST v11 and every cycle for safety using Common Terminology Criteria for Adverse Events CTCAE v40
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 |
|---|---|---|---|
| 14-C-0156 | None | None | None |