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

Dana-Farber Cancer Institute

Status and phase: Active, not recruiting; Phase 2

Conditions: Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer; HER-2 Positive Breast Cancer

Treatments: Procedure: Excision of tumor/mastectomy; Drug: Pertuzumab; Drug: T-DM1

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02326974

14-409

Details and patient eligibility

About

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

Full 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.

Enrollment: 164 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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164 participants in 1 patient group

T-DM1 and Pertuzumab

Experimental group

Description:

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.

Treatment:

Drug: T-DM1

Drug: Pertuzumab

Procedure: Excision of tumor/mastectomy