Ignite Creation Date:
2024-05-06 @ 5:33 PM
Last Modification Date:
2024-10-26 @ 2:30 PM
Study NCT ID:
NCT05340413
Status:
RECRUITING
Last Update Posted:
2023-04-18
First Post:
2022-01-25
Brief Title:
Predicting Olaparib Sensitivity in Patients With Unresectable Locally AdvancedMetastatic HER2-negative Breast Cancer
Sponsor:
SOLTI Breast Cancer Research Group
Organization:
SOLTI Breast Cancer Research Group
Study Overview
Official Title:
Predicting Olaparib Sensitivity in Patients With Unresectable Locally AdvancedMetastatic HER2-negative Breast Cancer With BRCA1 BRCA2 PALB2 RAD51C or RAD51D Mutations or RAD51-foci Low Test RADIOLA TRIAL
Status:
RECRUITING
Status Verified Date:
2023-04
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:
RADIOLA
Brief Summary:
The primary objetive is to assess the capacity of the RAD51-foci score to predict the efficacy of olaparib in BRCA12 PALB2 or RAD51CD mut advanced breast cancer cohort 1
The investigators propose the hypothesis that the RAD51-foci low tumours determined by immunofluorescence using RAD51 assay in patients with BRCA12 PALB2 RAD51CD mutation cohort 1 predicts response to olaparib Furthermore The investigators posit that the determination of RAD51-foci score in tumour identifies patients who can benefit from olaparib beyond mutations in these 5 genes This hypothesis will be tested in cohort 2
The investigators propose the hypothesis that the RAD51-foci low tumours determined by immunofluorescence using RAD51 assay in patients with BRCA12 PALB2 RAD51CD mutation cohort 1 predicts response to olaparib Furthermore The investigators posit that the determination of RAD51-foci score in tumour identifies patients who can benefit from olaparib beyond mutations in these 5 genes This hypothesis will be tested in cohort 2
Detailed Description:
This is an open-label single arm multicentre phase II study evaluating treatment with olaparib in patients with unresectable locally advanced or metastatic breast cancer MBC in two cohorts
1 with mutation in germlinesomatic BRCA12 PALB2 or RAD51CD and
2 RAD51-foci low score in wild type HRR tumours or without known deleterious BRCA12 PALB2 or RAD51CD mutations at study entry
Although efficacy and safety will be investigated The primary objective consists in identifying a predictive biomarker for clinical benefit of treatment with olaparib
All patients recruited in the study will be selected based on the following 3 principles
Genetic selection
Cohort 1 HER2-negative ABC with documented germline or somatic mutation in BRCA1 BRCA2 PALB2 RAD51C or RAD51D that is predicted to be deleterious or suspected deleterious known or predicted to be detrimentallead to loss of function Patients with BRCA1 BRCA2 PALB2 RAD51C or RAD51D mutations that are considered to be non-detrimental eg Variants of uncertain clinical significance or Variant of unknown significance or Variant favor polymorphism or benign polymorphism etc will not be eligible for this cohort
Cohort 2 HER2-negative ABC with RAD51-foci low score in the most recent locally recurrence or metastatic biopsy and without known or with negative germline or somatic mutation in BRCA1 BRCA2 PALB2 RAD51C or RAD51D predicted to be deleterious or suspected deleterious known or predicted to be detrimentallead to loss of function Mutation status will be assessed in at least olaparib responding patients in this subgroup
Phenotypic tumour selection Patients can have either triple-negative breast cancer defined as ER and PgR negative IHC nuclear staining 1 and HER2 negative IHC 0 1 or 2 andor ISH non-amplified with ratio less than 20 or ERPgR positive breast cancer as long as they are HER2 negative
Treatment setting
Patients with ER andor PgR positive breast cancer must have received and relapsedprogressed on at least one line of endocrine withwithout CDK46 inhibitors either in the neoadjuvant or advanced setting or are not considered appropriate for endocrine wwo CDK46i treatment
All patients should have unresectable locally advanced or metastatic breast cancer
No more than 2 prior lines of cytotoxic chemotherapy for advanced disease are allowed which means that to be eligible patients should be suitable for single agent chemotherapy in either 1st 2nd or 3rd line setting
Prior therapy with platinum for metastatic breast cancer is allowed provided there has been no evidence of disease progression during platinum treatment and the screening biopsy was performed after the end of treatment with the platinum-based antineoplastic drugs
In addition patients may have received prior platinum and or PARP inhibitors as potentially curative treatment for prior cancer eg ovarian cancer or as adjuvantneoadjuvant treatment for breast cancer as long as there is a period of at least 6 months between the last dose of platinum andor PARP inhibitors and start of study treatment
In cohort 1 patients will be enrolled according to their mutation status The most recent locally recurrencemetastatic sample will be requested to retrospectively assess the RAD51-foci score and correlate with treatment efficacy In cohort 2 patients will first undergo a pre-screening process with centralized determination of the quality of the sample assessment of the RAD51-foci score and eligibility After confirmation of all eligibility criteria eligible patients will receive olaparib 300 mg po twice daily Treatment will continue until disease progression as assessed by the investigator the development of unacceptable toxicity withdrawal of consent whichever occurs first
For estimation of overall response rate ORR clinical benefit rate CBR duration of response DoR and progression-free survival PFS tumour response will be based on RECIST v11 Tumour assessments will be performed every 8 weeks 56 days 1 week for the first 6 months then every 12 weeks 84 days 1 week until disease progression treatment discontinuation the start of new anti-cancer treatment withdrawal of consent death or the end of the study whichever occurs first Tumour assessments will be performed on the specified schedule regardless of treatment delays
Safety assessments will include the incidence nature and severity of adverse events AEs and laboratory abnormalities graded per the NCI CTCAE v5 Laboratory safety assessments will include the regular monitoring of haematology blood chemistry and pregnancy test Justification for dose The dose of olaparib used in this study is 300 mg twice daily which is the currently approved dose
1 with mutation in germlinesomatic BRCA12 PALB2 or RAD51CD and
2 RAD51-foci low score in wild type HRR tumours or without known deleterious BRCA12 PALB2 or RAD51CD mutations at study entry
Although efficacy and safety will be investigated The primary objective consists in identifying a predictive biomarker for clinical benefit of treatment with olaparib
All patients recruited in the study will be selected based on the following 3 principles
Genetic selection
Cohort 1 HER2-negative ABC with documented germline or somatic mutation in BRCA1 BRCA2 PALB2 RAD51C or RAD51D that is predicted to be deleterious or suspected deleterious known or predicted to be detrimentallead to loss of function Patients with BRCA1 BRCA2 PALB2 RAD51C or RAD51D mutations that are considered to be non-detrimental eg Variants of uncertain clinical significance or Variant of unknown significance or Variant favor polymorphism or benign polymorphism etc will not be eligible for this cohort
Cohort 2 HER2-negative ABC with RAD51-foci low score in the most recent locally recurrence or metastatic biopsy and without known or with negative germline or somatic mutation in BRCA1 BRCA2 PALB2 RAD51C or RAD51D predicted to be deleterious or suspected deleterious known or predicted to be detrimentallead to loss of function Mutation status will be assessed in at least olaparib responding patients in this subgroup
Phenotypic tumour selection Patients can have either triple-negative breast cancer defined as ER and PgR negative IHC nuclear staining 1 and HER2 negative IHC 0 1 or 2 andor ISH non-amplified with ratio less than 20 or ERPgR positive breast cancer as long as they are HER2 negative
Treatment setting
Patients with ER andor PgR positive breast cancer must have received and relapsedprogressed on at least one line of endocrine withwithout CDK46 inhibitors either in the neoadjuvant or advanced setting or are not considered appropriate for endocrine wwo CDK46i treatment
All patients should have unresectable locally advanced or metastatic breast cancer
No more than 2 prior lines of cytotoxic chemotherapy for advanced disease are allowed which means that to be eligible patients should be suitable for single agent chemotherapy in either 1st 2nd or 3rd line setting
Prior therapy with platinum for metastatic breast cancer is allowed provided there has been no evidence of disease progression during platinum treatment and the screening biopsy was performed after the end of treatment with the platinum-based antineoplastic drugs
In addition patients may have received prior platinum and or PARP inhibitors as potentially curative treatment for prior cancer eg ovarian cancer or as adjuvantneoadjuvant treatment for breast cancer as long as there is a period of at least 6 months between the last dose of platinum andor PARP inhibitors and start of study treatment
In cohort 1 patients will be enrolled according to their mutation status The most recent locally recurrencemetastatic sample will be requested to retrospectively assess the RAD51-foci score and correlate with treatment efficacy In cohort 2 patients will first undergo a pre-screening process with centralized determination of the quality of the sample assessment of the RAD51-foci score and eligibility After confirmation of all eligibility criteria eligible patients will receive olaparib 300 mg po twice daily Treatment will continue until disease progression as assessed by the investigator the development of unacceptable toxicity withdrawal of consent whichever occurs first
For estimation of overall response rate ORR clinical benefit rate CBR duration of response DoR and progression-free survival PFS tumour response will be based on RECIST v11 Tumour assessments will be performed every 8 weeks 56 days 1 week for the first 6 months then every 12 weeks 84 days 1 week until disease progression treatment discontinuation the start of new anti-cancer treatment withdrawal of consent death or the end of the study whichever occurs first Tumour assessments will be performed on the specified schedule regardless of treatment delays
Safety assessments will include the incidence nature and severity of adverse events AEs and laboratory abnormalities graded per the NCI CTCAE v5 Laboratory safety assessments will include the regular monitoring of haematology blood chemistry and pregnancy test Justification for dose The dose of olaparib used in this study is 300 mg twice daily which is the currently approved dose
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