Clinical Trial - NCT03716180

DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC

Recruiting

Sponsor: Dana-Farber Cancer Institute

Collaborators: Susan G. Komen Breast Cancer Foundation, Breast Cancer Research Foundation, Terri Brodeur Breast Cancer Foundation

Information provided by (Responsible party): Principal Investigator Dana-Farber Cancer Institute Adrienne G. Waks Principal Investigator

ClinicalTrials.gov Identifier: NCT03716180

Protocol Info

Short Description: DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC
Long Description: DAPHNe: De-escalation to adjuvant antibodies post-pCR to neoadjuvant THP (paclitaxel/trastuzumab/pertuzumab)-a pilot study in HER2-positive breast cancer
MGH Status: Open
Sponsor: DF/HCC
Disease Program: Breast

Next Steps


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Purpose

This research study is studying whether participants and their doctors are willing to determine post-surgery treatment on the basis of response to pre-surgery treatment, and studying blood and tissue collected from participants treated with a combination of drugs as a treatment for breast cancer. The names study drugs involved in this study are: - Paclitaxel (also called Taxol) - Trastuzumab (also called Herceptin) - Pertuzumab (also called Perjeta)
Condition Title Intervention Phase
Breast Cancer Paclitaxel Trastuzumab Pertuzumab Phase 1
Study Type Interventional
Official Title DAPHNe: De-escalation to Adjuvant Antibodies Post-pCR to Neoadjuvant THP (Paclitaxel/Trastuzumab/Pertuzumab)—a Pilot Study in HER2-positive Breast Cancer

Primary Outcome Measures

Adjuvant chemotherapy Received [Time Frame: 2.5 years] [Designated as safety issue: ]


Secondary Outcome Measures

pCR rate [Time Frame: 2 years] [Designated as safety issue: ]

Residual Cancer Burden (RCB) scores [Time Frame: 2 years] [Designated as safety issue: ]

Reasons for Off-Protocol Escalation per study-specific questionnaires [Time Frame: 2 years] [Designated as safety issue: ]

Reasons for Off-Protocol De-Escalation per study-specific questionnaires [Time Frame: 2 years] [Designated as safety issue: ]

One Year of Trastuzumab and Pertuzumab [Time Frame: 3 years] [Designated as safety issue: ]

Event-Free Survival (EFS) [Time Frame: 12 years] [Designated as safety issue: ]

Recurrence-Free Interval (RFI) [Time Frame: 12 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: 12 years] [Designated as safety issue: ]

Post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen [Time Frame: 2 years] [Designated as safety issue: ]

Estimated Enrollment: 100
Study Start Date: November 2018
Estimated Study Completion Date: September 2030
Estimated Primary Completion Date: January 2021
Arms Assigned Interventions

Experimental:Paclitaxel+Trastuzumab+Pertuzumab

Paclitaxel is administered intravenously on days 1, 8, and 15 of each 21-day cycle Trastuzumab is administered intravenously on day 1 of each 21-day cycle Pertuzumab is administered intravenously on Day 1 of each 21-day cycle
Drug:Pertuzumab
Pertuzumab is a monoclonal antibody which targets the surface of the cells human epidermal growth factor receptor 2 protein (HER2) on the cancer cell, interfering with HER2 causing cancer cell death

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Patients must have Stage II or III (according to AJCC cancer staging manual anatomic staging table, 8th edition) histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 1.5 cm determined by physical exam or imaging (whichever is larger) is required. Patients with inflammatory breast carcinoma (T4d) are NOT eligible.
  • Tumors must be HER-2 positive, as assessed by standard local institutional protocol (central testing is not required):
  • IHC 3+
  • 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 ratio <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. ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol.
  • Bilateral breast cancers are allowed as long as both cancers are HER2-positive (as defined in 3.1.2), or the contralateral cancer is a <1 cm, ER+, and HER2- tumor.
  • Patients with multifocal or multicentric disease are eligible as long as all tumor foci that were tested for HER2 status at the local institution are HER2-positive, and at least one tumor focus meets eligibility criteria.
  • Breast imaging should include dedicated ultrasound of the ipsilateral axilla. For subjects with a clinically positive axilla based on exam or imaging, a fine needle aspiration or core biopsy procedure will be performed to determine the presence of metastatic disease in the lymph nodes (though lymph node sampling procedure need not be resulted prior to patient's registration on trial, as long as all other eligibility are met).
  • Men and women (with any menopausal status) ≥ 18 years of age are eligible.
  • ECOG PS 0 or 1.
  • Required laboratory values:
  • ANC ≥ 1000/mm3
  • Hemoglobin ≥ 9 g/dl
  • Platelets ≥ 100,000/mm3
  • Serum creatinine < 1.5 x ULN (institutional) OR calculated GFR ≥60mL/min.
  • Total bilirubin ≤ 1.5 x ULN (institutional). For patients with Gilbert Syndrome, the direct bilirubin should be within the institutional normal range OR total bilirubin ≤ 2.0 mg/dL.
  • AST and ALT ≤ 2.5x ULN (institutional)
  • Left ventricular ejection fraction (LVEF) ≥ 50%.
  • Premenopausal women must have a negative serum pregnancy test within 14 days of registration, 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.
  • 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 registration.
  • 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) Class II or higher (see Appendix B), or serious cardiac arrhythmia requiring medication.
  • Significant symptoms (Grade ≥ 2) from 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03716180

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
    • DF/BWCC at Milford Regional Medical Center Milford, Massachusetts, United States, 01757
    • DF/BWCC in clinical affiliation with South Shore Hospital South Weymouth, Massachusetts, United States, 02190

Sponsors and Collaborators

Dana-Farber Cancer Institute

Susan G. Komen Breast Cancer Foundation

Breast Cancer Research Foundation

Terri Brodeur Breast Cancer Foundation

More Information

No publications provided

Responsible Party: Principal Investigator Dana-Farber Cancer Institute Adrienne G. Waks Principal Investigator
ClinicalTrials.gov Identifier: NCT03716180
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Dana-Farber Cancer Institute:

Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Pertuzumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019