Ignite Creation Date:
2024-05-06 @ 2:54 PM
Last Modification Date:
2024-10-26 @ 1:39 PM
Study NCT ID:
NCT04460430
Status:
TERMINATED
Last Update Posted:
2022-10-25
First Post:
2020-06-29
Brief Title:
Targeting EGFRERBB2 With Neratinib in Hormone Receptor HR-PositiveHER2-negative HER2-enriched AdvancedMetastatic Breast Cancer
Sponsor:
SOLTI Breast Cancer Research Group
Organization:
SOLTI Breast Cancer Research Group
Study Overview
Official Title:
Targeting EGFRERBB2 With Neratinib in Hormone Receptor HR-PositiveHER2-negative HER2-enriched AdvancedMetastatic Breast Cancer
Status:
TERMINATED
Status Verified Date:
2022-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
premature termination due to lack of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NEREA
Brief Summary:
HRHER2-negative BC represent 70 of all newly diagnosed breast tumours and are responsible for most recurrences and deaths due to this disease and despite available standard therapies 15-20 of hormone tumours recur at distant sites As BC is a clinically and biologically heterogeneous disease intrincsic subtype may play an important role in classifying patients In this case HER2-E subtype is present in approximately 66-110 of HRHER2-negative tumors and might express either HER2 estrogen receptor ER or progesterone receptor PR we also know that HER2-E is present twice as much in metastatic tumors compared to primary tumors and that HER2-E patients may benefit in terms of PFS form an anti-HER2 drug as was showed using retrospective sample in EGF30008 trial Therefore incorporation of novel drugs in combination with endocrine therapy ET can improve patient outcomes in HRHER2-negative BC advanced disease specially in those with HER2-E subtype
Methods NEREA is an open-label single arm multicenter phase II study evaluating treatment with neratinib in combination with ET in pre and post-menopausal women and men with locally advanced or metastatic HER2-enriched HER2-E HRHER2-negative breast cancer who had recurrence or progression while receiving previous ET either aromatase inhibitors tamoxifen or fulvestrant in the adjuvant setting or to treat advanced disease or both The study will follow a Simons 2-stage design with one interim and one final efficacy analysis The primary objective will is assess the efficacy of neratinib in combination with ET is this group of patients efficacy will be measured as Progression-Free Survival at 6 months PFS6 defined as the proportion of patients alive and without progression locally assessed by the investigator through the use of RECIST v11 at 24 weeks after first treatment administration imaging evaluation will be performed every 8 weeks for the first 12 months following treatment start and every 12 weeks thereafter Secondary endpoints include Clinical Benefit Rate at 6 months Overall Response rate Duration of response Time to response and Incidence duration and severity of Adverse Events The interim analysis will be conducted when 33 patients are evaluable for the primary endpoint having the potential for at least 3 on treatment disease assessment scans If less than 15 patients achieved a PFS6 the trial will be terminated for futility in favor of the null hypothesis If more than 28 patients achieved a PFS6 the trial will be stopped in favor of the alternative hypothesis demonstrating activity If none of the two above-mentioned conditions are attain up to a further 23 patients may be evaluated for at least a total of 56 evaluable patients Therefore if a total of 28 or more patients achieved a PFS6 at the end of the second stage then the null will be rejected in favor of the alternative
Eligible patients will receive neratinib 240 mg every day in combination with ET with either exemestane fulvestrant or tamoxifen exemestane 25 mg every day orally tamoxifen 20mg every day orally or fulvestrant 500 mg administered in two intramuscular injections of 250 mg each at C1D15 and at D1 of each subsequent 28-day cycle at investigator discretion LHRH agonist will be used in men and premenopausal women if no oophorectomy has been performed previously All patients will take prophylactic loperamide with a stablished doses scheme during the firs cycle and on demand in subsequent cycles
Methods NEREA is an open-label single arm multicenter phase II study evaluating treatment with neratinib in combination with ET in pre and post-menopausal women and men with locally advanced or metastatic HER2-enriched HER2-E HRHER2-negative breast cancer who had recurrence or progression while receiving previous ET either aromatase inhibitors tamoxifen or fulvestrant in the adjuvant setting or to treat advanced disease or both The study will follow a Simons 2-stage design with one interim and one final efficacy analysis The primary objective will is assess the efficacy of neratinib in combination with ET is this group of patients efficacy will be measured as Progression-Free Survival at 6 months PFS6 defined as the proportion of patients alive and without progression locally assessed by the investigator through the use of RECIST v11 at 24 weeks after first treatment administration imaging evaluation will be performed every 8 weeks for the first 12 months following treatment start and every 12 weeks thereafter Secondary endpoints include Clinical Benefit Rate at 6 months Overall Response rate Duration of response Time to response and Incidence duration and severity of Adverse Events The interim analysis will be conducted when 33 patients are evaluable for the primary endpoint having the potential for at least 3 on treatment disease assessment scans If less than 15 patients achieved a PFS6 the trial will be terminated for futility in favor of the null hypothesis If more than 28 patients achieved a PFS6 the trial will be stopped in favor of the alternative hypothesis demonstrating activity If none of the two above-mentioned conditions are attain up to a further 23 patients may be evaluated for at least a total of 56 evaluable patients Therefore if a total of 28 or more patients achieved a PFS6 at the end of the second stage then the null will be rejected in favor of the alternative
Eligible patients will receive neratinib 240 mg every day in combination with ET with either exemestane fulvestrant or tamoxifen exemestane 25 mg every day orally tamoxifen 20mg every day orally or fulvestrant 500 mg administered in two intramuscular injections of 250 mg each at C1D15 and at D1 of each subsequent 28-day cycle at investigator discretion LHRH agonist will be used in men and premenopausal women if no oophorectomy has been performed previously All patients will take prophylactic loperamide with a stablished doses scheme during the firs cycle and on demand in subsequent cycles
Detailed Description:
None
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2019-000710-11 | EUDRACT_NUMBER | None | None |