Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06613516
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-19
Brief Title:
Effect of Capivasertib on ctDNA in ER Positive Breast Cancer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
CaptAin - Effect of Capivasertib on ctDNA in ER Positive Breast Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
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:
CaptAin
Brief Summary:
There is growing evidence that cancer DNA called circulating tumour DNA - ctDNA in the blood is often an early sign that the cancer is likely to return The aim of this study is to investigate whether treating women who have detectable ctDNA in their blood with a drug called Capivasertib can help control ctDNA levels and prevent developing metastatic or secondary breast cancer
A recruitment of 20 women with oestrogen receptor ER positive breast cancer who are already on standard of care hormone therapy who are being treated with curative intent is aimed for which means that the disease has not yet spread to distant parts of the body Each subject will be dosed with 400mg of Capivasertib twice a day for a maximum period of two years
A recruitment of 20 women with oestrogen receptor ER positive breast cancer who are already on standard of care hormone therapy who are being treated with curative intent is aimed for which means that the disease has not yet spread to distant parts of the body Each subject will be dosed with 400mg of Capivasertib twice a day for a maximum period of two years
Detailed Description:
Early stage I-III ER positive HER2 negative breast cancer is treated with intensive multi-modal treatment which may include chemotherapy radiotherapy and endocrine therapy given with curative intent In spite of this 10-40 of patients will ultimately relapse with incurable metastatic disease which will be terminal and life limiting There is therefore a need to identify which patients are more at risk of relapse and develop strategies to alter the disease course in these patients
There is a now a body of evidence that circulating tumour DNA ctDNA can be detected in the blood of patients who are going to relapse and that detection of this ctDNA antecedes clinical recurrence by approximately 9 months Coombes et al Garcia-Murillas et al
This presents an ideal circumstance in which to intervene by considering ctDNA positive patients to have micrometastatic diseasemolecular relapse and treating them with agents designed to modify the otherwise predictable outcome of relapse and ultimately death from their disease
Capivasertib is a potent selective inhibitor of the kinase activity of the serinethreonine AktPKB protein kinase B that is being developed as a potential treatment for solid and haematological malignancies AZD5363 inhibits all three Akt isoforms and therefore has the potential to provide clinical benefit over a range of therapeutic indications
Given the recent success of Capivasertib in extending progression free survival in metastatic ER positive breast cancer FAKTION trial Jones et al it is proposed that treating ctDNA positive patients with this drug at this earlier stage may influence ctDNA levels and potentially the outcomes for these patients
It is porposed to identify a cohort of ctDNA positive patients and treat them with Capivasertib and monitor their ctDNA levels prospectively over time whilst following the patients for toxicity and clinical outcomes
Given that ctDNA positivity in ER positive breast cancer portends relapse whether Capivasertib affects ctDNA levels in patients who have detectable ctDNA will be established Moreover there is limited data on how ctDNA levels change over time especially in response to treatments and this study will offer valuable insights into that area which can feed into larger studies in the near future
It is proposed to screen a number of patients who have completed standard of care curative intent treatment for their ER positive breast cancer and are established on aromatase inhibitor therapy ampgt6 months and are planned to have ongoing endocrine therapy for at least another two years Patients meeting the inclusion criteria will be screened until 20 ctDNA positive patients have been enrolled The plan is to take blood at a single time point for each patient and will screen for ctDNA positivity using a personalised ctDNA assay as previously described Coombes et al Garcia-Murillas et al Commercially available Signatera assay will be used to determine ctDNA positivity Patients who are found to be ctDNA positive will then be started on treatment with Capivasertib and ctDNA levels will be followed over time If patients are ctDNA negative on their first ctDNA sample they will have an opportunity to be re-tested for ctDNA every 3 months until the end of the screening period which will end once 20 patients are recruited to start treatment This is based on data that shows that ctDNA positivity pick-up rate improves with serial testing in patients over time Coombes et al
The hypothesis is that treating these ctDNA positive patients with Capivasertib will have an effect on the dynamics of the ctDNA measurements Patients will also be followed over time to assess toxicity and acceptability of the drug and to monitor for overt metastatic relapse
The outcome measures of the study is
To monitor ctDNA dynamics during treatment with Capivasertib
Percentage of patients with ctDNA clearance compared to baseline
Duration of ctDNA clearance
Percentage of patients with gt50 decrease in ctDNA mean variant allele frequency VAF compared to baseline
There is a now a body of evidence that circulating tumour DNA ctDNA can be detected in the blood of patients who are going to relapse and that detection of this ctDNA antecedes clinical recurrence by approximately 9 months Coombes et al Garcia-Murillas et al
This presents an ideal circumstance in which to intervene by considering ctDNA positive patients to have micrometastatic diseasemolecular relapse and treating them with agents designed to modify the otherwise predictable outcome of relapse and ultimately death from their disease
Capivasertib is a potent selective inhibitor of the kinase activity of the serinethreonine AktPKB protein kinase B that is being developed as a potential treatment for solid and haematological malignancies AZD5363 inhibits all three Akt isoforms and therefore has the potential to provide clinical benefit over a range of therapeutic indications
Given the recent success of Capivasertib in extending progression free survival in metastatic ER positive breast cancer FAKTION trial Jones et al it is proposed that treating ctDNA positive patients with this drug at this earlier stage may influence ctDNA levels and potentially the outcomes for these patients
It is porposed to identify a cohort of ctDNA positive patients and treat them with Capivasertib and monitor their ctDNA levels prospectively over time whilst following the patients for toxicity and clinical outcomes
Given that ctDNA positivity in ER positive breast cancer portends relapse whether Capivasertib affects ctDNA levels in patients who have detectable ctDNA will be established Moreover there is limited data on how ctDNA levels change over time especially in response to treatments and this study will offer valuable insights into that area which can feed into larger studies in the near future
It is proposed to screen a number of patients who have completed standard of care curative intent treatment for their ER positive breast cancer and are established on aromatase inhibitor therapy ampgt6 months and are planned to have ongoing endocrine therapy for at least another two years Patients meeting the inclusion criteria will be screened until 20 ctDNA positive patients have been enrolled The plan is to take blood at a single time point for each patient and will screen for ctDNA positivity using a personalised ctDNA assay as previously described Coombes et al Garcia-Murillas et al Commercially available Signatera assay will be used to determine ctDNA positivity Patients who are found to be ctDNA positive will then be started on treatment with Capivasertib and ctDNA levels will be followed over time If patients are ctDNA negative on their first ctDNA sample they will have an opportunity to be re-tested for ctDNA every 3 months until the end of the screening period which will end once 20 patients are recruited to start treatment This is based on data that shows that ctDNA positivity pick-up rate improves with serial testing in patients over time Coombes et al
The hypothesis is that treating these ctDNA positive patients with Capivasertib will have an effect on the dynamics of the ctDNA measurements Patients will also be followed over time to assess toxicity and acceptability of the drug and to monitor for overt metastatic relapse
The outcome measures of the study is
To monitor ctDNA dynamics during treatment with Capivasertib
Percentage of patients with ctDNA clearance compared to baseline
Duration of ctDNA clearance
Percentage of patients with gt50 decrease in ctDNA mean variant allele frequency VAF compared to baseline
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None