T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA
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|ClinicalTrials.gov Identifier: NCT02326974|
Recruitment Status : Active, not recruiting
First Posted : December 30, 2014
Last Update Posted : January 15, 2019
This research study is studying a combination of drugs as a possible treatment for breast cancer that has tested positive for a protein called HER2.
The names of the study interventions involved in this study are:
- Trastuzumab emtansine (also called T-DM1)
|Condition or disease||Intervention/treatment||Phase|
|HER-2 Positive Breast Cancer Breast Cancer Stage II Breast Cancer Stage III Breast Cancer||Drug: T-DM1 Drug: Pertuzumab Procedure: Excision of tumor/mastectomy||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||164 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Impact of HER2 Heterogeneity on the Treatment of Early-stage HER2-positive Breast Cancer: a Phase II Study of T-DM1 in Combination With Pertuzumab in the Preoperative Setting|
|Actual Study Start Date :||December 29, 2014|
|Actual Primary Completion Date :||June 18, 2018|
|Estimated Study Completion Date :||April 2022|
Experimental: T-DM1 and Pertuzumab
T-DM1 via IV every 3 weeks for 6 doses and Pertuzumab loading dose via IV on Cycle 1 Day 1 followed by maintenance dose via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor
Participants will receive Trastuzumab emtansine (T-DM1) by IV every 3 weeks for 6 doses; for a total of 18 weeks of treatment.
Other Name: Kadcyla
Participants will receive a loading dose of pertuzumab by IV on Cycle 1 Day 1 followed by maintenance dose of pertuzumab by IV every 3 weeks for a total of 6 doses; for a total of 18 weeks of treatment.
Other Name: Perjeta
Procedure: Excision of tumor/mastectomy
Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.
- Pathologic complete response (pCR) [ Time Frame: 2 years ]Pathologic response is determined by Residual Cancer Burden (RCB) as RCB= 0.
- Intratumor heterogeneity of HER2 amplification [ Time Frame: 2 Years ]Intratumor heterogeneity will be assessed from two core biopsies at baseline from different geographic areas, and a dichotomous determination of heterogeneity will be made. HER2 genetic heterogeneity will be defined as the existence of an area of tumor cells with a HER2/CEP17 ratio ≥2.0 or a gene copy number of >6 and representing more than 5% but less than 50% of infiltrating tumor cells. HER2 regional heterogeneity will be defined as at least one of the six tumor areas being HER2 negative by ISH (HER2/CEP17 ratio <2 and CN <6, if IHC is <3+). A HER2-positive tumor will be considered HER2 heterogeneous if genetic heterogeneity and/or HER2 regional heterogeneity is identified
- Clinical response [ Time Frame: 2 Years ]Partial or complete response after preoperative T-DM1 plus pertuzumab
- Safety and tolerability of T-DM1 plus pertuzumab assessed by incidence of adverse events which will be reported by term and by maximum grade using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 2 Years ]
- Enrichment for HER2-negativity or HER2 heterogeneity in residual tumors treated with T-DM1 plus pertuzumab preoperative therapy [ Time Frame: 2 years ]Enrichment will be measured as absolute change in HER2-negativity and HER2 heterogeneity between residual tumors and baseline biopsies.
- Disease-free and overall survival in patient groups defined by HER2 heterogeneity who are treated with T-DM1 plus pertuzumab [ Time Frame: 2 years ]Disease-free survival is defined as the interval from the date of definitive surgery to disease recurrence. Overall survival is defined as the interval from the date of registration to death from any cause.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02326974
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Tennessee|
|Tennessee Oncology/Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Ian Krop, MD, PhD||Dana-Farber Cancer Institute|