T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA

NCT ID: NCT02326974

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2028-01-31

Brief 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

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

T-DM1

Intervention Type: DRUG

Neoadjuvant treatment is for a total of 18 weeks.

Pertuzumab

Intervention Type: DRUG

Neoadjuvant treatment is for a total of 18 weeks.

Excision of tumor/mastectomy

Intervention Type: PROCEDURE

Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.

Interventions

T-DM1

Neoadjuvant treatment is for a total of 18 weeks.

Intervention Type: DRUG

Pertuzumab

Neoadjuvant treatment is for a total of 18 weeks.

Intervention Type: DRUG

Excision of tumor/mastectomy

Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.

Intervention Type: PROCEDURE

Other Intervention Names

Kadcyla; Perjeta

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Otto Metzger, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Otto Metzger, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Tennessee Oncology/Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38300710 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

14-409

Identifier Type: -

Identifier Source: org_study_id