HER-2 Positive Breast CancerPhase 2NCT02326974
T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA
A Phase 2 study testing T-DM1, Pertuzumab and Excision of tumor/mastectomy in people with HER-2 Positive Breast Cancer and Breast Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
Trial summary
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) Pertuzumab Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER-2 Positive Breast Cancer, Breast Cancer, Stage II Breast Cancer
- What is being tested?
- T-DM1, Pertuzumab and Excision of tumor/mastectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2015to Jan 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have HER2-positive Stage II or III histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or imaging is required.
- HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH positive based on one of the three following criteria:
- Single-probe average HER2 copy number≥6.0 signals/cell OR
- Dual-probe HER2/CEP17 <2.0 with an average HER2 copy number ≥6.0 signals/cell OR
- Dual-probe HER2/CEP17 ratio ≥2.0
- ER/PR determination is required.
Show all 30Show fewer
- Bilateral breast cancers are allowed if both cancers are HER2-positive.
- Patients with multifocal or multicentric disease are eligible as long as one area meets eligibility criteria.
- Breast imaging should include the ipsilateral axilla. For subjects with a clinically negative axilla, a sentinel lymph node biopsy will be performed either before or after preoperative therapy at the discretion of the subject's physicians. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to determine the presence of metastatic disease in the lymph nodes.
- Men and women (with any menopausal status) ≥ 18 years of age
- ECOG performance status 0 or 1
- Required laboratory values:
- ANC ≥1500/mm3
- Hemoglobin ≥ 9 g/dl
- Platelets ≥100,000/mm3
- Serum creatinine < 1.5 X ULN (institutional)
- Total bilirubin ≤ 1.0 X ULN (institutional) For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range.
- AST and ALT ≤ 1.5x ULN (institutional)
- Alkaline phosphatase ≤1.5x ULN (institutional)
- Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B core antibody (HBcAb) in addition to HCV antibody testing.
- Only for patients who test positive for hep B/C virus: PTT/INR < ULN (institutional)
- Left ventricular ejection fraction (LVEF) ≥ 55%
- Premenopausal women must have a negative serum pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause.
- Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of study treatment.
- Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with T-DM1.
- Excessive alcohol intake should be avoided (occasional use is permitted).
- Patients with a history of ipsilateral DCIS are eligible.
- Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy.
- Willing and able to sign informed consent.
- Willing to provide tissue for research purposes.
Who cannot join
- Pregnant or nursing women due to the teratogenic potential of the study drugs.
- Active, unresolved infection.
- Receipt of intravenous antibiotics for infection within 7 days prior to enrollment.
- Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis.
- Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication.
- Significant symptoms (Grade ≥2) peripheral neuropathy.
- Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.
- Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Tennessee Oncology/Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
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
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)
- Pertuzumab
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for pre-operative use in breast cancer but it has been approved for other uses in breast cancer. The FDA has approved pertuzumab as a pre-operative treatment.
- Conditions
- HER-2 Positive Breast Cancer, Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer
- Being tested
- T-DM1, Pertuzumab, Excision of tumor/mastectomy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-DM1Drug
Also called Kadcyla
Neoadjuvant treatment is for a total of 18 weeks.
PertuzumabDrug
Also called Perjeta
Neoadjuvant treatment is for a total of 18 weeks.
Excision of tumor/mastectomyProcedure or surgery
Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.
| Study group | Role | What they receive |
|---|---|---|
| T-DM1 and Pertuzumab | Experimental | 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. Receives: Drug: T-DM1; Drug: Pertuzumab; Procedure: Excision of tumor/mastectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Pathologic Complete Response (pCR) by HER2 Amplification Status Non-Heterogeneous
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.
Measured: Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment.
Secondary outcomes (8)
Rate of Pathologic Complete Response (pCR)
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).
Measured: Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment.
Hormone Receptor (HR) Status by HER2 Amplification Status
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.
Measured: Day 0 (baseline/at study entry)
Median Disease-Free Survival
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.
Measured: Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10.
Median Overall Survival
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.
Measured: Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10.
Clinical Response Rate (Complete Response)
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
Measured: Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.
Clinical Response Rate (Partial Response)
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.
Measured: Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.
Number of Participants With a Dose Reduction
Number of participants with ever having dose reduction on neoadjuvant therapy up to surgery.
Measured: Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.
Treatment-Emergent Fatigue Rate
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.
Measured: Adverse events are assessed every cycle of neoadjuvant therapy prior to surgery, up to approximately 18 weeks (6 cycles) from study enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionJun 2018
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER-2 Positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Adrienne G. Waks, Dana-Farber Cancer Institute
- Investigators
- Adrienne Waks, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02326974
- Sponsor's protocol ID
- 14-409
- Status last verified
- Sep 2026
- First submitted
- 15 Dec 2014
- Last updated
- 2 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Li Z, Metzger Filho O, Viale G, dell'Orto P, Russo L, Goyette MA, Kamat A, Yardley DA, Gupta Abramson V, Arteaga CL, Spring LM, Chiotti K, Halsey C, Waks AG, King TA, Lester SC, Bellon JR, Winer EP, Spellman PT, Krop IE, Polyak K. HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial. J Clin Invest. 2024 Feb 1;134(7):e176454. doi: 10.1172/JCI176454.
PubMed 38300710