DTP: Durvalumab With Trastuzumab and Pertuzumab in HER2-Enriched Breast Cancer

Sponsor
The Methodist Hospital Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT03820141
Collaborator
AstraZeneca (Industry)
39
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40.9
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Study Details

Study Description

Brief Summary

The purpose of this research study is to test the safety and effectiveness of using durvalumab with trastuzumab and pertuzumab in participants with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The purpose of this research study is to test the safety and effectiveness of using durvalumab with trastuzumab and pertuzumab in participants with HER2-enriched breast cancer. The standard or usual pre-surgery treatment for this type of disease are drugs called trastuzumab and pertuzumab that target HER2. Studies have shown that trastuzumab and pertuzumab treatment can stimulate the body's own immune system to attack cancer cells. Durvalumab is a drug that also activates the immune system. The use of durvalumab together with trastuzumab and pertuzumab treatment may allow the immune system to work harder to kill cancer cells.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
39 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multicenter Phase II Trial of Durvalumab (MEDI4736) With Trastuzumab and Pertuzumab Combination in HER2-Enriched and HER2-Amplified Breast Cancer (DTP Trial)
Actual Study Start Date :
Mar 3, 2020
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Durvalumab + Trastuzumab + Pertuzumab

Durvalumab, trastuzumab, and pertuzumab will be administered on Day 1 every 3 weeks for 6 cycles. Trastuzumab will be administered as 8 mg/kg intravenous (IV) loading dose, followed by 6 mg/kg IV. Pertuzumab will be administered as 840 mg IV loading dose, followed by 420 mg. Durvalumab will be administered at a fixed dose of 1120 mg IV.

Drug: Durvalumab
programmed cell death-ligand 1 inhibitor
Other Names:
  • IMFINZI, MEDI4736
  • Drug: Trastuzumab
    anti-HER2 monoclonal antibody
    Other Names:
  • Herceptin
  • Drug: Pertuzumab
    anti-HER2 monoclonal antibody
    Other Names:
  • Perjeta
  • Outcome Measures

    Primary Outcome Measures

    1. Pathological complete response (pCR) rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer [18 weeks]

      Determine pCR rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer

    Secondary Outcome Measures

    1. pCR rate in the breast in patients whose tumors have <5% and ≥5% tumor-infiltrating lymphocytes (TILs) [18 weeks]

      Determine pCR rate in the breast in patients whose tumors have <5% and ≥5% TILs

    2. pCR rate in patients with programmed cell death-ligand 1 (PD-L1)-positive and PD-L1-negative tumors [18 weeks]

      Determine pCR rate in the breast in patients with PD-L1-positive and PD-L1-negative tumors

    3. Three-year disease-free survival (DFS) rate in patients who achieve pCR [3 years]

      Determination of 3-year DFS rate in patients who achieve pCR

    4. Number of participants with treatment-related adverse events [18 weeks]

      Number of participants with treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Female aged >18 years at the time of study entry.

    2. Histologically confirmed HER2-enriched (by BluePrint) and HER2-amplified (ERBB2 mRNA

    7.5-10) breast cancer.

    1. Estrogen receptor and progesterone receptor negative.

    2. Stage I or II disease.

    3. Node-negative breast cancer according to the American Joint Committee on Cancer 7th Edition.

    4. T2 disease.

    5. Bilateral breast cancers that individually meet eligibility criteria are allowed.

    6. Eastern Cooperative Oncology Group performance status of 0 or 1.

    7. Adequate organ and marrow function.

    8. Baseline left ventricular ejection fraction greater than or equal to 50%, as measured by multigated acquisition scan or echocardiogram.

    9. Evidence of postmenopausal status or negative serum pregnancy test for premenopausal patients. Negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to the first dose of study treatment for premenopausal patients.

    10. Willing to provide biopsy tissues as required by the study.

    11. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.

    Exclusion Criteria:
    1. Participation in another clinical study with an investigational product within 28 days prior to the first dose of study treatment.

    2. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

    3. Unresolved or unstable adverse events from prior administration of another investigational drug.

    4. Any concurrent chemotherapy, radiation therapy, immunotherapy, or biologic therapy for cancer treatment.

    5. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment.

    6. History of allogenic organ transplantation.

    7. Active or prior documented autoimmune or inflammatory disorders.

    8. Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase the risk of incurring adverse events, or compromise the ability of the patient to give written informed consent.

    9. History of another primary malignancy except for: malignancy treated with curative intent and with no known active disease for more than 5 years before the first dose of study treatment and of low potential risk for recurrence.

    10. History of active primary immunodeficiency.

    11. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.

    12. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment.

    13. Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.

    14. Patients who are pregnant or breastfeeding or patients of reproductive potential who are not willing to employ effective birth control from screening to 7 months after the last dose of study treatment.

    15. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Houston Methodist Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • The Methodist Hospital Research Institute
    • AstraZeneca

    Investigators

    • Principal Investigator: Jenny Chang, M.D., Houston Methodist Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jenny C. Chang, MD, Director, Houston Methodist Cancer Center, The Methodist Hospital Research Institute
    ClinicalTrials.gov Identifier:
    NCT03820141
    Other Study ID Numbers:
    • Pro00020917
    First Posted:
    Jan 29, 2019
    Last Update Posted:
    Aug 8, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 8, 2022