Ignite Creation Date:
2025-12-24 @ 9:44 PM
Ignite Modification Date:
2025-12-30 @ 9:54 PM
Study NCT ID:
NCT02789332
Status:
COMPLETED
Last Update Posted:
2020-03-17
First Post:
2016-05-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Assessing the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency
Sponsor:
GBG Forschungs GmbH
Organization:
Study Overview
Official Title:
A Randomized Phase II Trial to Assess the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency (HRD Patients With Deleterious BRCA1/2 Tumor or Germline Mutation and/or 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 PO→EC as neoadjuvant treatment of operable and locally advanced breast cancer in patients with HR deficiency. Patients will be randomized to receive
* paclitaxel 80 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or
* paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (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 mg/m² iv weekly in combination with olaparib tablets 100 mg (4X25mg) twice daily for 12 weeks (65 patients) or
* paclitaxel 80 mg/m² iv weekly in combination with carboplatin AUC 2 iv weekly for 12 weeks (37 patients) both followed by 4 cycles of epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (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 1/2 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 (ypT0/is ypN0 65%) and with HRD score high (ypT0/is 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 1/2 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 1/2 mutations and/or 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 (ypT0/is ypN0 65%) and with HRD score high (ypT0/is 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 1/2 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 1/2 mutations and/or HRD score high).
Study Oversight
Has Oversight DMC:
True
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?: