Ignite Creation Date:
2024-05-06 @ 2:15 PM
Last Modification Date:
2024-10-26 @ 1:28 PM
Study NCT ID:
NCT04266249
Status:
RECRUITING
Last Update Posted:
2024-04-18
First Post:
2020-02-07
Brief Title:
CompassHER2-pCR Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy
Sponsor:
ECOG-ACRIN Cancer Research Group
Organization:
Eastern Cooperative Oncology Group
Study Overview
Official Title:
CompassHER2-pCR Preoperative THP and Postoperative HP in Patients Who Achieve a Pathologic Complete Response
Status:
RECRUITING
Status Verified Date:
2024-04
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:
None
Brief Summary:
This trial studies how well paclitaxel trastuzumab and pertuzumab work in eliminating further chemotherapy after surgery in patients with HER2-positive stage II-IIIa breast cancer who have no cancer remaining at surgery either in the breast or underarm lymph nodes after pre-operative chemotherapy and HER2-targeted therapy Drugs used in chemotherapy such as paclitaxel work in different ways to stop the growth of tumor cells either by killing the cells by stopping them from dividing or by stopping them from spreading Trastuzumab and pertuzumab are both a form of targeted therapy because they work by attaching themselves to specific molecules receptors on the surface of tumor cells known as HER2 receptors When these drugs attach to HER2 receptors the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the bodys immune system Giving paclitaxel trastuzumab and pertuzumab may enable fewer chemotherapy drugs to be given without compromising patient outcomes compared to the usual treatment
Detailed Description:
PRIMARY OBJECTIVES
I To determine if 3-year recurrence-free survival RFS is greater than 92 among clinical stages II or IIIa patients with HER2-positive breast cancer who achieve pathologic complete response pCR ypT0is ypN0 after preoperative therapy with 12 weeks of a taxane trastuzumab or Food and Drug Administration FDA approved biosimilar and pertuzumab THP x 12
SECONDARY OBJECTIVES
I To determine 3-year IDFS invasive disease-free survival DDFS distant disease-free survival DRFS distant relapse-free survival RFI recurrence-free interval OS overall survival and breast cancer-specific survival in patients who achieve pCR and by pretreatment clinical stage Secondary Clinical Objective II To determine 3-year EFS event-free survival in all patients from time of study registration Secondary Clinical Objective III To evaluate safety and tolerability for all patients during the pre-operative phase and for patients who attain pCR and de-escalate therapy Arm A until the completion of post-surgery protocol assigned therapy ie until the end of trastuzumab and pertuzumab HP therapy Secondary Clinical Objective IV To evaluate the association of estrogen receptor ER status in the untreated primary tumor with pathologic response and with long-term survival outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Secondary Correlative Objective V To evaluate the associations of detection of circulating tumor cells CTCs in the blood at baseline with pCR Secondary Correlative Objective VI To evaluate the association of detection of CTCs in the blood at baseline after 3 weeks of THP after 12 weeks of THP before surgery after surgery before any additional therapy and after completion of HER2-targeted therapy with RFS in patients who achieve pCR or not Secondary Correlative Objective
EXPLORATORY OBJECTIVES
I To determine 3-year RFS IDFS invasive disease-free survival DDFS distant disease-free survival DRFS distant relapse-free survival RFI recurrence-free interval OS overall survival and breast cancer-specific survival in patients who do not achieve pCR and by pretreatment clinical stage Exploratory Clinical Objective II To determine the pathologic response to THP neoadjuvant therapy as assessed by residual cancer burden RCB Exploratory Clinical Objective III To determine the association between residual cancer burden RCB and all described standardized definitions for efficacy end points STEEP criteria outcomes Exploratory Clinical Objective IV To determine the false negative rate FNR of limited staging procedures defined as sentinel lymph node biopsy SLNB plus removal of clipped node in patients who undergo such procedures with a planned axillary lymph node dissection ALND Exploratory Clinical Objective V To determine axillary pCR rates as a function of the burden of disease at presentation as determined on pre-treatment ultrasound US and the axillary staging technique SLNB plus ensuring removal of clipped node versus ALND Exploratory Clinical Objective VI To evaluate the associations between plasma tumor cell-free deoxyribonucleic acid DNA cfDNA tumor-specific mutations baseline and after therapy with pathologic response and long-term outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Exploratory Correlative Objective VII To evaluate the associations between tumor infiltrating lymphocytes TILs and immune activation gene signatures in the baseline tumor with pathologic response and long-term outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Exploratory Correlative Objective VIII To determine the frequency of change in intrinsic subtype between pretreatment tumor specimen and residual disease at the time of surgery Exploratory Correlative Objective IX To evaluate the associations between DNA copy number DNA mutations ribonucleic acid RNA expression and protein expression in the baseline tumor and changes from baseline to post-THP therapy with pathologic response and long-term outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Exploratory Correlative Objective
OUTLINE
PRE-OPERATIVENEOADJUVANT THERAPY Patients receive either paclitaxel or nab-paclitaxel intravenously IV on days 1 8 and 15 or docetaxel IV on day 1 at the discretion of the treating oncologist Patients also receive trastuzumab IV on day 1 or days 1 8 and 15 and pertuzumab IV on day 1 Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
SURGERY Within 42 days after last dose of neoadjuvant therapy patients undergo standard of care lumpectomy andor mastectomy
POST-OPERATIVEADJUVANT THERAPY Patients are assigned to 1 of 2 arms
ARM A Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1 Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate
ARM B Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity Patients may also receive additional standard of care chemotherapy as well as hormone therapy if appropriate
After completion of study treatment patients are followed up every 3 months for 2 years every 6 months for 2-5 years then annually for 5-15 years from date of surgery
I To determine if 3-year recurrence-free survival RFS is greater than 92 among clinical stages II or IIIa patients with HER2-positive breast cancer who achieve pathologic complete response pCR ypT0is ypN0 after preoperative therapy with 12 weeks of a taxane trastuzumab or Food and Drug Administration FDA approved biosimilar and pertuzumab THP x 12
SECONDARY OBJECTIVES
I To determine 3-year IDFS invasive disease-free survival DDFS distant disease-free survival DRFS distant relapse-free survival RFI recurrence-free interval OS overall survival and breast cancer-specific survival in patients who achieve pCR and by pretreatment clinical stage Secondary Clinical Objective II To determine 3-year EFS event-free survival in all patients from time of study registration Secondary Clinical Objective III To evaluate safety and tolerability for all patients during the pre-operative phase and for patients who attain pCR and de-escalate therapy Arm A until the completion of post-surgery protocol assigned therapy ie until the end of trastuzumab and pertuzumab HP therapy Secondary Clinical Objective IV To evaluate the association of estrogen receptor ER status in the untreated primary tumor with pathologic response and with long-term survival outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Secondary Correlative Objective V To evaluate the associations of detection of circulating tumor cells CTCs in the blood at baseline with pCR Secondary Correlative Objective VI To evaluate the association of detection of CTCs in the blood at baseline after 3 weeks of THP after 12 weeks of THP before surgery after surgery before any additional therapy and after completion of HER2-targeted therapy with RFS in patients who achieve pCR or not Secondary Correlative Objective
EXPLORATORY OBJECTIVES
I To determine 3-year RFS IDFS invasive disease-free survival DDFS distant disease-free survival DRFS distant relapse-free survival RFI recurrence-free interval OS overall survival and breast cancer-specific survival in patients who do not achieve pCR and by pretreatment clinical stage Exploratory Clinical Objective II To determine the pathologic response to THP neoadjuvant therapy as assessed by residual cancer burden RCB Exploratory Clinical Objective III To determine the association between residual cancer burden RCB and all described standardized definitions for efficacy end points STEEP criteria outcomes Exploratory Clinical Objective IV To determine the false negative rate FNR of limited staging procedures defined as sentinel lymph node biopsy SLNB plus removal of clipped node in patients who undergo such procedures with a planned axillary lymph node dissection ALND Exploratory Clinical Objective V To determine axillary pCR rates as a function of the burden of disease at presentation as determined on pre-treatment ultrasound US and the axillary staging technique SLNB plus ensuring removal of clipped node versus ALND Exploratory Clinical Objective VI To evaluate the associations between plasma tumor cell-free deoxyribonucleic acid DNA cfDNA tumor-specific mutations baseline and after therapy with pathologic response and long-term outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Exploratory Correlative Objective VII To evaluate the associations between tumor infiltrating lymphocytes TILs and immune activation gene signatures in the baseline tumor with pathologic response and long-term outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Exploratory Correlative Objective VIII To determine the frequency of change in intrinsic subtype between pretreatment tumor specimen and residual disease at the time of surgery Exploratory Correlative Objective IX To evaluate the associations between DNA copy number DNA mutations ribonucleic acid RNA expression and protein expression in the baseline tumor and changes from baseline to post-THP therapy with pathologic response and long-term outcomes including RFS EFS IDFS DDFS DRFS RFI OS and breast cancer-specific survival Exploratory Correlative Objective
OUTLINE
PRE-OPERATIVENEOADJUVANT THERAPY Patients receive either paclitaxel or nab-paclitaxel intravenously IV on days 1 8 and 15 or docetaxel IV on day 1 at the discretion of the treating oncologist Patients also receive trastuzumab IV on day 1 or days 1 8 and 15 and pertuzumab IV on day 1 Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity
SURGERY Within 42 days after last dose of neoadjuvant therapy patients undergo standard of care lumpectomy andor mastectomy
POST-OPERATIVEADJUVANT THERAPY Patients are assigned to 1 of 2 arms
ARM A Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1 Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate
ARM B Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity Patients may also receive additional standard of care chemotherapy as well as hormone therapy if appropriate
After completion of study treatment patients are followed up every 3 months for 2 years every 6 months for 2-5 years then annually for 5-15 years from date of surgery
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 |
|---|---|---|---|
| NCI-2019-07439 | REGISTRY | None | None |
| EA1181 | OTHER | None | None |
| EA1181 | OTHER | None | None |
| U10CA180820 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180820 |