Clinical Trials /

Durvalumab With Trastuzumab and Pertuzumab in HER2-Enriched Breast Cancer

NCT03820141

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab With Trastuzumab and Pertuzumab in HER2-Enriched Breast Cancer
  • Official Title: Multicenter Phase II Trial of Durvalumab (MEDI4736) With Trastuzumab and Pertuzumab Combination in HER2-Enriched and HER2-Amplified Breast Cancer (DTP Trial)

Clinical Trial IDs

  • ORG STUDY ID: Pro00020917
  • NCT ID: NCT03820141

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
DurvalumabIMFINZI, MEDI4736Durvalumab + Trastuzumab + Pertuzumab
TrastuzumabHerceptinDurvalumab + Trastuzumab + Pertuzumab
PertuzumabPerjetaDurvalumab + Trastuzumab + Pertuzumab

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Durvalumab + Trastuzumab + PertuzumabExperimentalDurvalumab, 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.
  • Durvalumab
  • Trastuzumab
  • Pertuzumab

Eligibility Criteria

        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.

          3. Estrogen receptor and progesterone receptor negative.

          4. Stage I or II disease.

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

          6. T2 disease.

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

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

          9. Adequate organ and marrow function.

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

         11. 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.

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

         13. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological complete response (pCR) rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer
Time Frame:18 weeks
Safety Issue:
Description:Determine pCR rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer

Secondary Outcome Measures

Measure:pCR rate in the breast in patients whose tumors have <5% and ≥5% tumor-infiltrating lymphocytes (TILs)
Time Frame:18 weeks
Safety Issue:
Description:Determine pCR rate in the breast in patients whose tumors have <5% and ≥5% TILs
Measure:pCR rate in patients with programmed cell death-ligand 1 (PD-L1)−positive and PD-L1−negative tumors
Time Frame:18 weeks
Safety Issue:
Description:Determine pCR rate in the breast in patients with PD-L1−positive and PD-L1−negative tumors
Measure:Three-year disease-free survival (DFS) rate in patients who achieve pCR
Time Frame:3 years
Safety Issue:
Description:Determination of 3-year DFS rate in patients who achieve pCR
Measure:Number of participants with treatment-related adverse events
Time Frame:18 weeks
Safety Issue:
Description:Number of participants with treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jenny C. Chang, MD

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