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

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ClinicalTrials.gov Identifier: NCT03716180
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : December 31, 2018
Sponsor:
Collaborators:
Susan G. Komen Breast Cancer Foundation
Breast Cancer Research Foundation
Terri Brodeur Breast Cancer Foundation
Information provided by (Responsible Party):
Adrienne G. Waks, Dana-Farber Cancer Institute

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)

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Paclitaxel Drug: Trastuzumab Drug: Pertuzumab Phase 1

Detailed Description:

This research study is a Pilot Study, which means investigators are looking at the feasibility of a new approach for deciding the optimal medical treatment for this type of breast cancer. The FDA (the U.S. Food and Drug Administration) has approved paclitaxel, trastuzumab, and pertuzumab as part of a pre-operative treatment option for this disease.

The purpose of this study is to evaluate whether participants and their doctors are willing to accept a treatment recommendation for post-operative chemotherapy, on the basis of the participant's response to pre-operative treatment with paclitaxel, trastuzumab, and pertuzumab.

In addition, the investigators are evaluating how the body's immune system works with paclitaxel, trastuzumab, and pertuzumab to kill cancer cells. For this reason, the investigators will collect samples of the participant's breast tumor and samples of the participant's blood over time to understand the reaction of the immune system to the participant's tumor.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: DAPHNe: De-escalation to Adjuvant Antibodies Post-pCR to Neoadjuvant THP (Paclitaxel/Trastuzumab/Pertuzumab)—a Pilot Study in HER2-positive Breast Cancer
Actual Study Start Date : November 5, 2018
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : September 1, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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: Paclitaxel
Paclitaxel is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug
Other Name: Taxol

Drug: Trastuzumab
Trastuzumab works by targeting the HER2/neu receptor on cancer cells
Other Name: Herceptin

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
Other Name: Perjeta




Primary Outcome Measures :
  1. Adjuvant chemotherapy Received [ Time Frame: 2.5 years ]
    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).


Secondary Outcome Measures :
  1. pCR rate [ Time Frame: 2 years ]
    To assess pathologic complete response (pCR) for 1) all patients, 2) hormone receptor positive (HR+) patients, and 3) hormone receptor negative (HR-) patients

  2. Residual Cancer Burden (RCB) scores [ Time Frame: 2 years ]
    To assess residual cancer burden (RCB) in 1) all patients, 2) hormone receptor positive patients (HR+), 3) hormone receptor negative (HR-) patients. RCB is scored from 0 to 3, (with possible values 0, 1, 2, 3), where 0 is the best score and indicates eradication of all disease at the time of surgery, and 3 is the worst score, indicating poor response to preoperative therapy.

  3. Reasons for Off-Protocol Escalation per study-specific questionnaires [ Time Frame: 2 years ]
    Patients and physicians will complete questionnaires to assess reasons for off-protocol escalation (meaning, a decision to administer post-operative chemotherapy, for patients with pCR). Standardized questionnaires for both patients and physician reviewers have been developed specifically for this study. Responses are qualitative and do not involve a scale.

  4. Reasons for Off-Protocol De-Escalation per study-specific questionnaires [ Time Frame: 2 years ]
    Patients and physicians will complete questionnaires to assess reasons for off-protocol de-escalation (meaning, a decision not to administer post-operative chemotherapy, for patients without pCR). Standardized questionnaires for both patients and physician reviewers have been developed specifically for this study. Responses are qualitative and do not involve a scale.

  5. One Year of Trastuzumab and Pertuzumab [ Time Frame: 3 years ]
    To assess the percentage of patients completing one year of HP

  6. Event-Free Survival (EFS) [ Time Frame: 12 years ]
    To measure event-free survival (EFS), and to compare EFS in the following subgroups: 1) Patients with pCR versus patients without pCR; 2) Patients with RCB 0 or 1, versus patients with RCB 2 or 3

  7. Recurrence-Free Interval (RFI) [ Time Frame: 12 years ]
    To measure recurrence-free interval (RFI), and to compare RFI in the following subgroups: 1) Patients with pCR versus patients without pCR; 2) Patients with RCB 0 or 1, versus patients with RCB 2 or 3

  8. Overall survival (OS) [ Time Frame: 12 years ]
    To measure overall survival (OS) as an exploratory endpoint

  9. Post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen [ Time Frame: 2 years ]
    To evaluate correlation between post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03716180


Contacts
Contact: Adrienne G Waks, MD 617-632-3800 awaks@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Laura Spring, MD       lspring2@partners.org   
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Neelam Desai, MD    617-667-7081    ndesai@bidmc.harvard.edu   
Principal Investigator: Neelam Desai, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Adrienne G Waks, MD    617-632-3800    awaks@partners.org   
Principal Investigator: Adrienne G Waks, MD         
DF/BWCC at Milford Regional Medical Center Recruiting
Milford, Massachusetts, United States, 01757
Contact: Michael Constantine, MD       michael_constantine@dfci.harvard.edu   
DF/BWCC in clinical affiliation with South Shore Hospital Recruiting
South Weymouth, Massachusetts, United States, 02190
Contact: Meredith Faggen, MD       meredith_faggen@dfci.harvard.edu   
Sponsors and Collaborators
Dana-Farber Cancer Institute
Susan G. Komen Breast Cancer Foundation
Breast Cancer Research Foundation
Terri Brodeur Breast Cancer Foundation
Investigators
Principal Investigator: Adrienne G Waks, MD Dana-Farber Cancer Institute

Responsible Party: Adrienne G. Waks, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03716180     History of Changes
Other Study ID Numbers: 18-394
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: December 31, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Adrienne G. Waks, Dana-Farber Cancer Institute:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Pertuzumab
Albumin-Bound Paclitaxel
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action