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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03716180
Recruitment Status : Active, not recruiting
First Posted : October 23, 2018
Last Update Posted : June 1, 2020
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

Tracking Information
First Submitted Date  ICMJE October 19, 2018
First Posted Date  ICMJE October 23, 2018
Last Update Posted Date June 1, 2020
Actual Study Start Date  ICMJE November 5, 2018
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2018)
  • 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
  • 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.
  • 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.
  • 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.
  • One Year of Trastuzumab and Pertuzumab [ Time Frame: 3 years ]
    To assess the percentage of patients completing one year of HP
  • 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
  • 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
  • Overall survival (OS) [ Time Frame: 12 years ]
    To measure overall survival (OS) as an exploratory endpoint
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2018)
  • 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
  • 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.
  • Reasons for Off-Protocol Escalation or De-Escalation [ 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) or de-escalation (meaning, a decision not to administer post-operative chemotherapy, for patients without pCR)
  • One Year of Trastuzumab and Pertuzumab [ Time Frame: 3 years ]
    To assess the percentage of patients completing one year of HP
  • 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
  • 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
  • Overall survival (OS) [ Time Frame: 12 years ]
    To measure overall survival (OS) as an exploratory endpoint
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC
Official Title  ICMJE DAPHNe: De-escalation to Adjuvant Antibodies Post-pCR to Neoadjuvant THP (Paclitaxel/Trastuzumab/Pertuzumab)—a Pilot Study in HER2-positive Breast Cancer
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)
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Interventions:
  • Drug: Paclitaxel
  • Drug: Trastuzumab
  • Drug: Pertuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 19, 2018)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2030
Estimated Primary Completion Date January 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03716180
Other Study ID Numbers  ICMJE 18-394
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Adrienne G. Waks, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE
  • Susan G. Komen Breast Cancer Foundation
  • Breast Cancer Research Foundation
  • Terri Brodeur Breast Cancer Foundation
Investigators  ICMJE
Principal Investigator: Adrienne G Waks, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP