Ignite Creation Date:
2024-05-06 @ 3:19 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04595565
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-17
First Post:
2020-04-07
Brief Title:
Sacituzumab Govitecan in Primary HER2-negative Breast Cancer
Sponsor:
German Breast Group
Organization:
German Breast Group
Study Overview
Official Title:
Phase III Postneoadjuvant Study Evaluating Sacituzumab Govitecan an Antibody Drug Conjugate in Primary HER2-negative Breast Cancer Patients With High Relapse Risk After Standard Neoadjuvant Treatment - SASCIA
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-06
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:
SASCIA
Brief Summary:
Phase III prospective multi-center randomized open label parallel group study in patients with HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy with 11 allocation to
Arm A Sacituzumab govitecan days 1 8 q3w for eight cycles
Arm B treatment of physicians choice TPC defined as capecitabine or platinum-based chemotherapy for eight cycles or observation
Treatment in either arm will be given for eight cycles
In patients with HR-positive breast cancer endocrine-based therapy which includes the use of CDK46 inhibitors will be administered according to local guidelines The start of endocrine therapy will be at the discretion of the investigator however it will be encouraged to start after surgeryradiotherapy in patients without additional cytotoxic agents
Adjuvant pembrolizumab can be given until the completion of radiotherapy before randomization Within the study the use of pembrolizumab in patients with TNBC who received pembrolizumab as neoadjuvant therapy is allowed as monotherapy in the TPC arm according to the approval of pembrolizumab in this setting
Arm A Sacituzumab govitecan days 1 8 q3w for eight cycles
Arm B treatment of physicians choice TPC defined as capecitabine or platinum-based chemotherapy for eight cycles or observation
Treatment in either arm will be given for eight cycles
In patients with HR-positive breast cancer endocrine-based therapy which includes the use of CDK46 inhibitors will be administered according to local guidelines The start of endocrine therapy will be at the discretion of the investigator however it will be encouraged to start after surgeryradiotherapy in patients without additional cytotoxic agents
Adjuvant pembrolizumab can be given until the completion of radiotherapy before randomization Within the study the use of pembrolizumab in patients with TNBC who received pembrolizumab as neoadjuvant therapy is allowed as monotherapy in the TPC arm according to the approval of pembrolizumab in this setting
Detailed Description:
Neoadjuvant chemotherapy NACT allows monitoring of tumor response to treatment and a pathological complete response pCR is associated with superior survival This association is strongest in the most aggressive subtype ie in patients with triple-negative breast cancer TNBC Patients with TNBC not achieving a pCR have a 5-year event free survival rate of about 50 The association between pCR and prognosis is less pronounced in HR-positiveHER2-negative patients However the CPSEG scoring system for prognosis after neoadjuvant chemotherapy taking into account clinical stage post treatment pathological stage estrogen receptor status and grade leads to an improved estimate of prognosis allowing to select patients at high risk of relapse for post-neoadjuvant therapy Patients with TNBC not achieving a pCR as well as those with HR-positiveHER2-negative tumors and a CPSEG score of 3 or 2ypN are at high risk of relapse warranting additional experimental therapies after NACT
There is proof of concept that post-neoadjuvant therapy can significantly improve survival First data was provided by the CREATE X trial randomizing patients with residual tumor after neoadjuvant chemotherapy to either capecitabine or observation CREATE X included HER2-negative patients and demonstrated a significant improvement in disease-free survival DFS and overall survival OS in the overall population which was confined to the TNBC subgroup
Recently the randomized post-neoadjuvant phase III KATHERINE study demonstrated an improved invasive disease-free survival in HER2-positive patients without pCR after trastuzumab - pertuzumab treated postoperatively with T-DM1 an antibody-drug-conjugate compared to trastuzumab
Sacituzumab govitecan has demonstrated unprecedented activity in heavily pretreated patients with metastatic triple-negative and HR-positiveHER2-negative breast cancer even after prior immune-checkpoint inhibitors or CDK46 and mTOR inhibitors Based on the results of the phase III study sacituzumab govitecan was granted a breakthrough therapy designation for the treatment of patients with advanced or metastatic TNBC who have received at least two previous lines of treatment for metastatic disease The efficacy of sacituzumab govitecan in advanced TNBC was confirmed in the phase III ASCENT trial Based on this study sacituzumab govitecan received regular approval Additionally the TROPiCS-02 study showed an improvement in progression-free survival and OS over single-agent chemotherapy and a manageable safety profile in patients with heavily pre-treated HR-positiveHER2-negative endocrine-resistant unresectable locally advanced or metastatic BC
There is proof of concept that post-neoadjuvant therapy can significantly improve survival First data was provided by the CREATE X trial randomizing patients with residual tumor after neoadjuvant chemotherapy to either capecitabine or observation CREATE X included HER2-negative patients and demonstrated a significant improvement in disease-free survival DFS and overall survival OS in the overall population which was confined to the TNBC subgroup
Recently the randomized post-neoadjuvant phase III KATHERINE study demonstrated an improved invasive disease-free survival in HER2-positive patients without pCR after trastuzumab - pertuzumab treated postoperatively with T-DM1 an antibody-drug-conjugate compared to trastuzumab
Sacituzumab govitecan has demonstrated unprecedented activity in heavily pretreated patients with metastatic triple-negative and HR-positiveHER2-negative breast cancer even after prior immune-checkpoint inhibitors or CDK46 and mTOR inhibitors Based on the results of the phase III study sacituzumab govitecan was granted a breakthrough therapy designation for the treatment of patients with advanced or metastatic TNBC who have received at least two previous lines of treatment for metastatic disease The efficacy of sacituzumab govitecan in advanced TNBC was confirmed in the phase III ASCENT trial Based on this study sacituzumab govitecan received regular approval Additionally the TROPiCS-02 study showed an improvement in progression-free survival and OS over single-agent chemotherapy and a manageable safety profile in patients with heavily pre-treated HR-positiveHER2-negative endocrine-resistant unresectable locally advanced or metastatic BC
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