Ignite Creation Date:
2024-05-06 @ 10:08 AM
Last Modification Date:
2024-10-26 @ 12:25 PM
Study NCT ID:
NCT03177187
Status:
TERMINATED
Last Update Posted:
2023-07-13
First Post:
2017-05-26
Brief Title:
Combination Study of AZD5069 and Enzalutamide
Sponsor:
Institute of Cancer Research United Kingdom
Organization:
Institute of Cancer Research United Kingdom
Study Overview
Official Title:
ACE Proof of Concept Phase III Trial of the CXCR2 Antagonist AZD5069 Administered in Combination with Enzalutamide in Patients with Metastatic Castration Resistant Prostate Cancer mCRPC
Status:
TERMINATED
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Discontinuation of production of IMP
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACE
Brief Summary:
ACE is a multi-centre proof of concept Phase III trial of the CXCR2 antagonist AZD5069 administered in combination with enzalutamide in patients with metastatic castration resistant prostate cancermCRPC The investigators will be investigating the safety and toxicity of the combination
Detailed Description:
The purpose of this study is to find out the side effects and safety of a combination of the CXCR2 antagonist AZD5069 in combination with the androgen receptor antagonist enzalutamide in patients with metastatic castration resistant prostate cancer and to determine the most appropriate dose of this combination During the phase I study patients will receive AZD5069 orally twice daily BD in combination with enzalutamide at 160mg orally once daily continuously The starting dose of AZD5069 will be 40mg BD dose level 1 other doses to be evaluated will include 80mg BD dose level 2 120mg BD dose level 3 160mg BD dose level 4 and 320mg BD dose level 5 in order to determine the MTD and RP2D to take forward to a Phase II reversal of resistance cohort Intermediate dose levels such as 240mg BD may also be evaluated During dose levels 1 to 4 patients will start with AZD5069 monotherapy for two weeks before commencing the combination At all other dose levels the two agents will be started concurrently In addition if agreed by the SRC intermediate dose levels such as 240 mg taken BD will be explored The Phase II part of the study will evaluate the optimized doseschedule identified in Phase I of the study in patients with metastatic castration resistant prostate cancer
In the Phase I part of the study the AZD5069 is started first and will be taken twice daily as an oral tablet at Cycle 1 Day -14 for 14 days Two weeks later on Cycle 1 Day 1 patients will start taking 160mg enzalutamide once a day in addition to the AZD5069 The starting dose of AZD5069 will be 40mg taken orally twice daily with single dose escalations to 80mg 120mg and 160mg taken orally twice daily to determine the MTD to take forward to a Phase II reversal of resistance cohort
The Phase II reversal of enzalutamide resistance study will explore whether the addition of AZD5069 to enzalutamide reverses resistance to enzalutamide alone In the phase II reversal of enzalutamide resistance study patients will start taking the AZD5069 at the dose established in the Phase I safety run in part of the study in combination with 160mg of enzalutamide once a day and at the same time from Cycle 1 Day 1 onwards
If the MTD of AZD5069 is greater than 160 mg BD two different dose levels may be taken forward to the phase II study to determine efficacy Only patients who have experienced disease progression after at least 12 weeks of treatment with enzalutamide apalutamide or darolutamide will be eligible for this trial Those patients who progressed on enzalutamide apalutamide or darolutamide at least 12 weeks of therapy greater than 6 months prior to starting the IMP will enter the Phase II enzalutamide resistance run in cohort to confirm resistance to enzalutamide once progression on enzalutamide is confirmed they will enter the Phase II reversal of enzalutamide resistance cohort
Up to approximately 86 patients will be enrolled into this phase III trial with up to 36 patients in the phase I safety run in cohort depending on number of patients required to determine the RP2D and up to 50 patients in the phase II study We predict around 50 of these patients will enter the phase II enzalutamide resistance run in cohort first The anticipated accrual rate for this trial is 3-6 patients per month across 4 centres
In the Phase I part of the study the AZD5069 is started first and will be taken twice daily as an oral tablet at Cycle 1 Day -14 for 14 days Two weeks later on Cycle 1 Day 1 patients will start taking 160mg enzalutamide once a day in addition to the AZD5069 The starting dose of AZD5069 will be 40mg taken orally twice daily with single dose escalations to 80mg 120mg and 160mg taken orally twice daily to determine the MTD to take forward to a Phase II reversal of resistance cohort
The Phase II reversal of enzalutamide resistance study will explore whether the addition of AZD5069 to enzalutamide reverses resistance to enzalutamide alone In the phase II reversal of enzalutamide resistance study patients will start taking the AZD5069 at the dose established in the Phase I safety run in part of the study in combination with 160mg of enzalutamide once a day and at the same time from Cycle 1 Day 1 onwards
If the MTD of AZD5069 is greater than 160 mg BD two different dose levels may be taken forward to the phase II study to determine efficacy Only patients who have experienced disease progression after at least 12 weeks of treatment with enzalutamide apalutamide or darolutamide will be eligible for this trial Those patients who progressed on enzalutamide apalutamide or darolutamide at least 12 weeks of therapy greater than 6 months prior to starting the IMP will enter the Phase II enzalutamide resistance run in cohort to confirm resistance to enzalutamide once progression on enzalutamide is confirmed they will enter the Phase II reversal of enzalutamide resistance cohort
Up to approximately 86 patients will be enrolled into this phase III trial with up to 36 patients in the phase I safety run in cohort depending on number of patients required to determine the RP2D and up to 50 patients in the phase II study We predict around 50 of these patients will enter the phase II enzalutamide resistance run in cohort first The anticipated accrual rate for this trial is 3-6 patients per month across 4 centres
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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