Ignite Creation Date:
2024-05-06 @ 6:33 PM
Last Modification Date:
2024-10-26 @ 2:50 PM
Study NCT ID:
NCT05708235
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-12
First Post:
2023-01-12
Brief Title:
A PoC Study to Evaluate Treatments Efficacy by Monitoring MRD Using ctDNA in HR-positiveHER2-negative EBC Population
Sponsor:
MedSIR
Organization:
MedSIR
Study Overview
Official Title:
A Proof of Concept Study to Evaluate Treatments Efficacy by Monitoring Minimal Residual Disease Using ctDNA in HR-positiveHER2-negative Early Breast Cancer Population
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-02
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:
MiRaDoR
Brief Summary:
This trial is a multicenter open-label non-comparative phase II biomarker-driven adjuvant treatment study involving the periodic collection and analysis of blood samples from patients with HR-positiveHER2-negative early-stage BC at higher risk of relapse who have undergone surgery within the previous five years with no evidence of locoregional contralateral or distant disease
The study design is composed by an initial pre-screening phase a molecular follow-up phase ctDNA surveillance phase and an interventional therapeutic phase treatment phase
After informed consent is obtained a total of1260 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel tumor signature
At the event of ctDNA positivity patients will be screened to enter the treatment phase of the study Upon confirmed eligibility a total of 40 patients will be allocated in one of the following trials arms adopting a sequential recruitment strategy
Arm A Control Arm N10 Arm B Experimental Arm with giredestrant N10 Arm C Experimental Arm with giredestrant abemaciclib N10 Arm D Experimental Arm with giredestrant inavolisib N10
If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome new cohorts may be added to the study
The study design is composed by an initial pre-screening phase a molecular follow-up phase ctDNA surveillance phase and an interventional therapeutic phase treatment phase
After informed consent is obtained a total of1260 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel tumor signature
At the event of ctDNA positivity patients will be screened to enter the treatment phase of the study Upon confirmed eligibility a total of 40 patients will be allocated in one of the following trials arms adopting a sequential recruitment strategy
Arm A Control Arm N10 Arm B Experimental Arm with giredestrant N10 Arm C Experimental Arm with giredestrant abemaciclib N10 Arm D Experimental Arm with giredestrant inavolisib N10
If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome new cohorts may be added to the study
Detailed Description:
This is a multicenter open-label non-comparative phase II biomarker-driven adjuvant treatment study involving the periodic collection and analysis of blood samples from patients with HR-positiveHER2-negative early-stage BC at higher risk of relapse who have undergone surgery within the previous five years with no evidence of locoregional contralateral or distant disease Patients must be on adjuvant treatment with ET for at least two years and no more than four years at the time of study enrolment with an additional three years of ET planned At least 12 months prior to enrolment on the same ET treatment AI or tamoxifen For pre-menopausal women and men LHRH is required
The trial design entails an initial pre-screening phase a molecular follow-up phase ctDNA surveillance phase and an interventional therapeutic phase treatment phase
After informed consent is obtained 1260 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel tumor signature
Note Additional patients may enter the ctDNA surveillance phase if needed for example if additional arms are opened
Then blood will be collected processed and analyzed to detect the presence or absence of ctDNA at predefined time points for longitudinal surveillance ctDNA analysis will occur every three months from study inclusion during the first year and every six months thereafter until positive result or end of accrual
At the event of ctDNA positivity patients will be screened to enter the treatment phase of the study Upon confirmed eligibility a total of 40 patients will be allocated in one of the following trials arms adopting a sequential recruitment strategy
Arm A Control Arm N10 Patients must continue the same standard ET prescribed as per standard practice used in the surveillance phase Changes in ET are not allowed
Arm B Experimental Arm with giredestrant N10
Giredestrant 30 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Arm C Experimental Arm with giredestrant abemaciclib N10
Giredestrant 30 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Abemaciclib 150 mg will be taken PO BID two intakes for a total daily dose of 300 mg during each 28-day cycle up to two years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Arm D Experimental Arm with giredestrant inavolisib N10
Giredestrant 30 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Inavolisib 9 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to two years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Note I In addition to the treatments described on each of the treatment arms LHRH agonist will be administered to male participants and premenopausalperimenopausal participants according to local prescribing information The patient should be supplied with the previous LHRH they were taking
Note II During the length of the study additional treatment arms may open to stay up to date with the most recent advances in oncology and to be able to provide the best treatment options to patients in this study Because of that the N of patients screened to enter the treatment phase may increase
In the meanwhile serial assessment of ctDNA will be continuously performed every three months during the first year and every six months thereafter until EoS to correlate any ctDNA variations with response
Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and new anti-cancer therapy information will be collected every three months 14 days from the last dose of study treatment up to the EoS Telephone contact is acceptable in some countries medical information can only be shared directly in person with the patient
Arm extensions
After initiation of study treatments data obtained from serial assessment of ctDNA will also be used to confirm feasibility of eventual arms extensions with maximum two arms that could be expanded 10 additional patients will be enrolled in each of the selected arms The expansion will be approved when the arm complies with the following criteria
If at three months a 90 ctDNA decrease is observed in at least 30 patients and if after three additional months a 90 ctDNA decrease is maintained in at least 20 patients In this case 10 additional patients will be enrolled in the specific experimental arms that meet these requirements N20
If all three experimental arms fulfill the criteria the two arms with the highest proportion of patients with the highest proportion of 90 decrease will be the ones expanded
If cohorts remain too similar no clear winners the decision will be taken by the Steering Committee based on the duration of the response and the safety and toxicity of each specific treatment
If none of the arms fulfill the specific expansion criteria the Steering Committee will evaluate the data further and may nominate the two arms with the strongest signal of ctDNA decreases for further expansion
If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome new cohorts may be added to the study
The trial design entails an initial pre-screening phase a molecular follow-up phase ctDNA surveillance phase and an interventional therapeutic phase treatment phase
After informed consent is obtained 1260 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel tumor signature
Note Additional patients may enter the ctDNA surveillance phase if needed for example if additional arms are opened
Then blood will be collected processed and analyzed to detect the presence or absence of ctDNA at predefined time points for longitudinal surveillance ctDNA analysis will occur every three months from study inclusion during the first year and every six months thereafter until positive result or end of accrual
At the event of ctDNA positivity patients will be screened to enter the treatment phase of the study Upon confirmed eligibility a total of 40 patients will be allocated in one of the following trials arms adopting a sequential recruitment strategy
Arm A Control Arm N10 Patients must continue the same standard ET prescribed as per standard practice used in the surveillance phase Changes in ET are not allowed
Arm B Experimental Arm with giredestrant N10
Giredestrant 30 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Arm C Experimental Arm with giredestrant abemaciclib N10
Giredestrant 30 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Abemaciclib 150 mg will be taken PO BID two intakes for a total daily dose of 300 mg during each 28-day cycle up to two years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Arm D Experimental Arm with giredestrant inavolisib N10
Giredestrant 30 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to five years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Inavolisib 9 mg will be administered PO QD on Days 1 to 28 of each 28-day cycle up to two years or until disease recurrence unacceptable toxicity or treatmentstudy discontinuation whichever occurs first
Note I In addition to the treatments described on each of the treatment arms LHRH agonist will be administered to male participants and premenopausalperimenopausal participants according to local prescribing information The patient should be supplied with the previous LHRH they were taking
Note II During the length of the study additional treatment arms may open to stay up to date with the most recent advances in oncology and to be able to provide the best treatment options to patients in this study Because of that the N of patients screened to enter the treatment phase may increase
In the meanwhile serial assessment of ctDNA will be continuously performed every three months during the first year and every six months thereafter until EoS to correlate any ctDNA variations with response
Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and new anti-cancer therapy information will be collected every three months 14 days from the last dose of study treatment up to the EoS Telephone contact is acceptable in some countries medical information can only be shared directly in person with the patient
Arm extensions
After initiation of study treatments data obtained from serial assessment of ctDNA will also be used to confirm feasibility of eventual arms extensions with maximum two arms that could be expanded 10 additional patients will be enrolled in each of the selected arms The expansion will be approved when the arm complies with the following criteria
If at three months a 90 ctDNA decrease is observed in at least 30 patients and if after three additional months a 90 ctDNA decrease is maintained in at least 20 patients In this case 10 additional patients will be enrolled in the specific experimental arms that meet these requirements N20
If all three experimental arms fulfill the criteria the two arms with the highest proportion of patients with the highest proportion of 90 decrease will be the ones expanded
If cohorts remain too similar no clear winners the decision will be taken by the Steering Committee based on the duration of the response and the safety and toxicity of each specific treatment
If none of the arms fulfill the specific expansion criteria the Steering Committee will evaluate the data further and may nominate the two arms with the strongest signal of ctDNA decreases for further expansion
If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome new cohorts may be added to the study
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