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

NCT03716180 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18-394
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

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)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Adjuvant chemotherapy Received

  To assess adherence to protocol-specified antibody doublet therapy in the adjuvant setting among patients with stage II-III HER2+ breast cancer who achieve pathologic complete response (pCR) following neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab (THP).

  2.5 years

Secondary Outcomes (9)

• pCR rate

  2 years

• Residual Cancer Burden (RCB) scores

  2 years

• Reasons for Off-Protocol Escalation per study-specific questionnaires

  2 years

• Reasons for Off-Protocol De-Escalation per study-specific questionnaires

  2 years

• One Year of Trastuzumab and Pertuzumab

  3 years

Study Arms (1)

Paclitaxel+Trastuzumab+Pertuzumab

EXPERIMENTAL

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: Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Paclitaxel DRUG

Paclitaxel is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug

Also known as: Taxol

Paclitaxel+Trastuzumab+Pertuzumab

Trastuzumab DRUG

Trastuzumab works by targeting the HER2/neu receptor on cancer cells

Also known as: Herceptin

Paclitaxel+Trastuzumab+Pertuzumab

Pertuzumab DRUG

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

Also known as: Perjeta

Paclitaxel+Trastuzumab+Pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Susan G. Komen Breast Cancer Foundation: collaborator
• Breast Cancer Research Foundation: collaborator
• Terri Brodeur Breast Cancer Foundation: collaborator

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

DF/BWCC at Milford Regional Medical Center

Milford, Massachusetts, 01757, United States

Location

DF/BWCC in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

Related Publications (2)

• Weiss A, Li T, Desai NV, Tung NM, Poorvu PD, Partridge AH, Nakhlis F, Dominici L, Sinclair N, Spring LM, Faggen M, Constantine M, Krop IE, DeMeo M, Wrabel E, Alberti J, Chikarmane S, Tayob N, King TA, Tolaney SM, Winer EP, Mittendorf EA, Waks AG. Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial. J Am Coll Surg. 2023 Aug 1;237(2):247-256. doi: 10.1097/XCS.0000000000000761. Epub 2023 May 17.

  PMID: 37194964 DERIVED

• Waks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O, Alberti J, Deane J, Rosenberg SM, Frank E, Tolaney SM, Krop IE, Tung NM, Tayob N, King TA, Mittendorf EA, Winer EP. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022 May 10;8(1):63. doi: 10.1038/s41523-022-00429-7.

  PMID: 35538105 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Adrienne G Waks, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: October 23, 2018
• Study Start: November 5, 2018
• Primary Completion: October 8, 2020
• Study Completion (Estimated): September 1, 2030
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)