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
Results First Posted : May 11, 2021
Last Update Posted : March 8, 2022
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 :||January 2015|
|Actual Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||January 2028|
Experimental: T-DM1 and Pertuzumab
T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy.
Neoadjuvant treatment is for a total of 18 weeks.
Other Name: Kadcyla
Neoadjuvant treatment is for a total of 18 weeks.
Other Name: Perjeta
Procedure: Excision of tumor/mastectomy
Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.
- Rate of Pathologic Complete Response (pCR) by HER2 Amplification Status Non-Heterogeneous [ Time Frame: Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment. ]
The rate of pCR is the percentage of participants with Residual Cancer Burden (RCB)=0 as defined by established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB).
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Rate of Pathologic Complete Response (pCR) [ Time Frame: Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment. ]The rate of pCR is the percentage of participants with Residual Cancer Burden (RCB)=0 as defined by established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB).
- Hormone Receptor (HR) Status by HER2 Amplification Status [ Time Frame: Day 0 (baseline/at study entry) ]HR status classified by estrogen receptor (ER) and/or progesterone receptor (ER) positive versus ER negative and PR negative determined by immunohistochemical methods according to the local institution's standard protocol.
- Median Disease-Free Survival [ Time Frame: Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10. ]Disease-free survival (DFS) based on the Kaplan-Meier method is defined as the duration of time from study entry to the occurrence of the first of the following events: local/regional recurrence, contralateral invasive breast cancer, distant recurrence or death from any cause. In situ cancer is not included as DFS event. Participants alive without an event are censored at date of last disease assessment.
- Median Overall Survival [ Time Frame: Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10. ]Overall survival (OS) based on Kaplan-Meier methods is defined as the interval from the date of registration to death from any cause. Patients are censored at date last known alive.
- Clinical Response Rate (Complete Response) [ Time Frame: Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment. ]Clinical response rate was defined as the percentage of participants achieving complete response (CR) based on RECIST 1.1 criteria on treatment up to surgery. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions
- Clinical Response Rate (Partial Response) [ Time Frame: Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment. ]Clinical response rate was defined as the percentage of participants achieving partial response (PR) based on RECIST 1.1 criteria on treatment up to surgery. Per RECIST 1.1 for target lesions: PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
- Number of Participants With a Dose Reduction [ Time Frame: Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment. ]Number of participants with ever having dose reduction on neoadjuvant therapy up to surgery.
- Treatment-Emergent Fatigue Rate [ Time Frame: Adverse events are assessed every cycle of neoadjuvant therapy prior to surgery, up to approximately 18 weeks (6 cycles) from study enrollment. ]Treatment-emergent fatigue rate is the percentage of participants who experienced grade 1-2 fatigue based on the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 as reported on the adverse event case report form. CTCAE severity scale ranges from 0 (none) to 5 (death): Grade 1=mild and Grade 2=moderate.
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:||Otto Metzger, MD||Dana-Farber Cancer Institute|