Ignite Creation Date:
2024-05-06 @ 8:38 AM
Last Modification Date:
2024-10-26 @ 12:03 PM
Study NCT ID:
NCT02789332
Status:
COMPLETED
Last Update Posted:
2020-03-17
First Post:
2016-05-23
Brief Title:
Assessing the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel Carboplatin Followed by EpirubicinCyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency
Sponsor:
German Breast Group
Organization:
German Breast Group
Study Overview
Official Title:
A Randomized Phase II Trial to Assess the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel Carboplatin Followed by EpirubicinCyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency HRD Patients With Deleterious BRCA12 Tumor or Germline Mutation andor HRD Score High
Status:
COMPLETED
Status Verified Date:
2020-03
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:
GeparOla
Brief Summary:
This is a multicenter prospective randomized open-label phase II study evaluating the efficacy and safety of POEC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency Patients will be randomized to receive
paclitaxel 80 mgm² iv weekly in combination with olaparib tablets 100 mg 4X25mg twice daily for 12 weeks 65 patients or
paclitaxel 80 mgm² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks 37 patients both followed by 4 cycles of epirubicin 90 mgm² and cyclophosphamide 600 mgm² EC either every 3 or every 2 weeks followed by surgery
The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen
paclitaxel 80 mgm² iv weekly in combination with olaparib tablets 100 mg 4X25mg twice daily for 12 weeks 65 patients or
paclitaxel 80 mgm² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks 37 patients both followed by 4 cycles of epirubicin 90 mgm² and cyclophosphamide 600 mgm² EC either every 3 or every 2 weeks followed by surgery
The control arm was chosen to allow direct comparison with one of the currently considered standard of care regimen
Detailed Description:
The efficacy of olaparib in germline HRD score high with or without BRCA 12 mutation carriers with breast cancer is not well described
The efficacy and safety of olaparib included in a standard of care regimen like paclitaxel weekly followed by epirubicin and cyclophosphamide Pw--EC is unknown
Carboplatin increased the pCR rate in patients with triple-negative breast cancer TNBC in two randomized phase II neoadjuvant studies when added to an anthracycline cyclophosphamide and paclitaxel GeparSixto CALBG 40603 pCR rates were even higher in patients with germline BRCA 1 or 2 mutations ypT0is ypN0 65 and with HRD score high ypT0is ypN0 63
The TNT study showed a doubling in response rate for patients receiving carboplatin vs docetaxel in patients with germline BRCA 1 or 2 mutations
There is a high correlation between tumor and germline BRCA 12 mutations
Data from Geparsixto study showed that triple negative breast patients have an HR deficiency in about 70 67 have a high HRD and 30 have a tBRCA mutation
About 5 of tBRCA patients have a low HRD score
gBRCA2 patients are older when diagnosed and are more likely to have an HRpos tumor
The GeparOLA study aims to support the decision for a phase III study exploring the addition of olaparib to a Pw--EC schedule by providing an estimate on the pCR rate in the targeted population but also by providing estimate comparison to paclitaxel and carboplatin followed by epirubicin and cyclophosphamide PCb--EC as carboplatin is more and more considered a standard option of care in HR deficient patients tBRCA 12 mutations andor HRD score high
The efficacy and safety of olaparib included in a standard of care regimen like paclitaxel weekly followed by epirubicin and cyclophosphamide Pw--EC is unknown
Carboplatin increased the pCR rate in patients with triple-negative breast cancer TNBC in two randomized phase II neoadjuvant studies when added to an anthracycline cyclophosphamide and paclitaxel GeparSixto CALBG 40603 pCR rates were even higher in patients with germline BRCA 1 or 2 mutations ypT0is ypN0 65 and with HRD score high ypT0is ypN0 63
The TNT study showed a doubling in response rate for patients receiving carboplatin vs docetaxel in patients with germline BRCA 1 or 2 mutations
There is a high correlation between tumor and germline BRCA 12 mutations
Data from Geparsixto study showed that triple negative breast patients have an HR deficiency in about 70 67 have a high HRD and 30 have a tBRCA mutation
About 5 of tBRCA patients have a low HRD score
gBRCA2 patients are older when diagnosed and are more likely to have an HRpos tumor
The GeparOLA study aims to support the decision for a phase III study exploring the addition of olaparib to a Pw--EC schedule by providing an estimate on the pCR rate in the targeted population but also by providing estimate comparison to paclitaxel and carboplatin followed by epirubicin and cyclophosphamide PCb--EC as carboplatin is more and more considered a standard option of care in HR deficient patients tBRCA 12 mutations andor HRD score high
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