Clinical Trials /

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

NCT03716180

Description:

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)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC
  • Official Title: DAPHNe: De-escalation to Adjuvant Antibodies Post-pCR to Neoadjuvant THP (Paclitaxel/Trastuzumab/Pertuzumab)—a Pilot Study in HER2-positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-394
  • NCT ID: NCT03716180

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PaclitaxelTaxolPaclitaxel+Trastuzumab+Pertuzumab
TrastuzumabHerceptinPaclitaxel+Trastuzumab+Pertuzumab
PertuzumabPerjetaPaclitaxel+Trastuzumab+Pertuzumab

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)

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.
    

Trial Arms

NameTypeDescriptionInterventions
Paclitaxel+Trastuzumab+PertuzumabExperimentalPaclitaxel 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
  • Paclitaxel
  • Trastuzumab
  • Pertuzumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adjuvant chemotherapy Received
Time Frame:2.5 years
Safety Issue:
Description: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

Measure:pCR rate
Time Frame:2 years
Safety Issue:
Description:To assess pathologic complete response (pCR) for 1) all patients, 2) hormone receptor positive (HR+) patients, and 3) hormone receptor negative (HR-) patients
Measure:Residual Cancer Burden (RCB) scores
Time Frame:2 years
Safety Issue:
Description: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.
Measure:Reasons for Off-Protocol Escalation or De-Escalation
Time Frame:2 years
Safety Issue:
Description: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)
Measure:One Year of Trastuzumab and Pertuzumab
Time Frame:3 years
Safety Issue:
Description:To assess the percentage of patients completing one year of HP
Measure:Event-Free Survival (EFS)
Time Frame:12 years
Safety Issue:
Description: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
Measure:Recurrence-Free Interval (RFI)
Time Frame:12 years
Safety Issue:
Description: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
Measure:Overall survival (OS)
Time Frame:12 years
Safety Issue:
Description:To measure overall survival (OS) as an exploratory endpoint
Measure:Post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen
Time Frame:2 years
Safety Issue:
Description:To evaluate correlation between post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer

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