Clinical Trials /

Study of Immunotherapy in Combination With Chemotherapy in HER2-negative Inflammatory Breast Cancer

NCT03515798

Description:

This phase II multicentre randomized open-label study will assess the safety and efficacy of Pembrolizumab in combination with standard chemotherapy in inflammatory breast cancer. Pembrolizumab will be administered every 3 weeks during the neoadjuvant chemotherapy. Tissue and blood samples will be collected pre- and post-treatment for translational research.

Related Conditions:
  • Inflammatory Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Immunotherapy in Combination With Chemotherapy in HER2-negative Inflammatory Breast Cancer
  • Official Title: A Prospective Multicenter Open-label, Randomized Phase II Study of Pembrolizumab in Combination With Neoadjuvant (F)EC-Paclitaxel Regimen in HER2-negative Inflammatory Breast Cancer.

Clinical Trial IDs

  • ORG STUDY ID: PELICAN-IPC 2015-016
  • SECONDARY ID: 2016-001868-11
  • NCT ID: NCT03515798

Conditions

  • Inflammatory Breast Cancer

Interventions

DrugSynonymsArms
Pembrolizumab InjectionMK3475Pembrolizumab
neoadjuvant (F)EC-paclitaxel chemotherapy5-Fluorouracil, Epirubicine, CyclophosphamidePembrolizumab

Purpose

This phase II multicentre randomized open-label study will assess the safety and efficacy of Pembrolizumab in combination with standard chemotherapy in inflammatory breast cancer. Pembrolizumab will be administered every 3 weeks during the neoadjuvant chemotherapy. Tissue and blood samples will be collected pre- and post-treatment for translational research.

Detailed Description

      Inflammatory breast cancer (IBC) is a rare and highly aggressive subtype of locally advanced
      breast cancer representing approximately 5% of all breast cancers that requires immediate
      aggressive treatment. Significant progress has been made in recent years using a combination
      of treatments, including neoadjuvant chemotherapy, surgery and radiation therapy.

      Accumulating data indicate a prognostic and/or predictive impact for immune-response
      variables in BC. Recent data, suggest that PD-L1 is overexpressed in a significant number of
      BC, notably in IBC and may have significant prognostic or predictive value. Furthermore it
      may be targeted to restore or boost functional antitumor immunity. Pembrolizumab, a
      PD-1-directed monoclonal antibody is already registered and has an out-standing activity in
      advanced melanoma and NSCLC patients, with promising results in several other tumor types,
      including triple-negative BC, and a favorable profile of tolerance.

      Thus, potential benefits of pembrolizumab in combination with a conventional cytotoxic
      backbone may be considered as high in HER2-negative IBC.

      The aim of the study is to assess the pathological complete response rate following
      neoadjuvant (F)EC-paclitaxel chemotherapy plus pembrolizumab and to assess if neoadjuvant
      chemotherapy with anthracycline-based induction in combination with pembrolizumab exposes IBC
      patients to significant toxicity. rates.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimental(F)EC Paclitaxel + Pembrolizumab Injection
  • Pembrolizumab Injection
  • neoadjuvant (F)EC-paclitaxel chemotherapy
Standard neoadjuvant chemotherapyActive Comparator(F)EC Paclitaxel alone
  • neoadjuvant (F)EC-paclitaxel chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          1. 18 years or older,

          2. Performance status 0 to 2,

          3. Able to comply with the protocol,

          4. Patient affiliated to the national "Social Security" regimen or beneficiary of this
             regimen,

          5. Patient must have signed a written informed consent form prior to any study specific
             screening procedures,

          6. Previously untreated, histologically confirmed breast cancer and confirmed
             inflammatory breast cancer defined as follows:

             - T4d any N following American Joint Committee on Cancer (AJCC)-7th version
             classification: diffuse Erythema and edema ("peau d'orange") of the breast, occupying
             at least 1/3 of the breast, with or without underlying palpable mass

          7. HER2 negative tumors by immunohistochemistry (IHC 0 or 1+) or fluorescent/chromogenic
             in situ hybridization (FISH- or CISH-)

          8. Hormone receptors status known,

          9. No metastases,

         10. Adequate hematologic function: absolute neutrophil count ≥ 1.2 x 109/L AND platelets ≥
             100 x 109 AND Hb ≥ 9 g/dL,

         11. Adequate liver function: total bilirubin ≤ 1.5 ULN unless elevation is due to
             Gilbert's disease or similar syndrome involving slow conjugation of bilirubin AND -
             ASAT < 2.5 ULN AND ALAT < 2.5 ULN,

         12. Adequate kidney function: serum creatinine ≤ 1.25 ULN or creatinine clearance ≥ 50
             mL/min according to the Cockcroft and Gault formula AND no proteinuria (> 1 g/24
             hours),

         13. Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% (isotopic
             or ultrasound methods),

         14. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 ULN AND normal TCA
             unless subject is receiving anticoagulant therapy, as long as PT or TCA is within
             therapeutic range of intended use of the anticoagulants,

         15. Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication. Subjects of
             child bearing potential are those who have not been surgically sterilized or have not
             been free from menses for >1 year. Note: Abstinence is acceptable if this is the
             established and preferred contraception for the subject,

         16. Female subject of childbearing potential should have a negative urine or serum
             preg-nancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required,

         17. Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

        Exclusion Criteria:

          1. Has metastatic breast cancer,

          2. Has HER2-positive breast cancer,

          3. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment,

          4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment,

          5. Has a known history of active TB (Bacillus Tuberculosis),

          6. Hypersensitivity to pembrolizumab or any of its excipients,

          7. If subject received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting therapy,

          8. Has a known additional malignancy that progressed or required treatment in the last 5
             years, Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma
             of the skin that has undergone potentially curative therapy or in situ cervical
             cancer,

          9. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment,

         10. Has history of/active pneumonitis requiring treatment with steroids or has history
             of/active interstitial lung disease,

         11. Has an active infection requiring systemic therapy.

         12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator,

         13. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial,

         14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment,

         15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent,

         16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies),

         17. Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected),

         18. Has received a live vaccine within 30 days of planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Central evaluation of pathological complete response rate
Time Frame:Following completion of neoadjuvant systemic treatment, an average of 24 weeks
Safety Issue:
Description:absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of NAST (i.e., ypT0/is, ypN0 in the current AJCC staging system)

Secondary Outcome Measures

Measure:occurrence of serious adverse events and adverse events starting grade 2 or grade 1 (run-in period)
Time Frame:during 21 days following the first administration of pembrolizumab
Safety Issue:
Description:according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.03
Measure:Local evaluation of pathological complete response rate
Time Frame:Following completion of neoadjuvant systemic treatment, an average of 24 weeks
Safety Issue:
Description:defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of NAST (i.e., ypT0/is, ypN0 in the current AJCC staging system)
Measure:Invasive disease-free survival (IDFS)
Time Frame:3 years
Safety Issue:
Description:time from surgery to the first documented occurrence of an event, defined as: Ipsilateral invasive breast tumor recurrence, Ipsilateral local-regional invasive breast cancer recurrence, Distant recurrence, Contralateral invasive breast cancer, Death from any cause
Measure:Invasive disease-free survival (IDFS)
Time Frame:5 years
Safety Issue:
Description:time from surgery to the first documented occurrence of an event, defined as: Ipsilateral invasive breast tumor recurrence, Ipsilateral local-regional invasive breast cancer recurrence, Distant recurrence, Contralateral invasive breast cancer, Death from any cause
Measure:Event free survival (EFS)
Time Frame:3 years
Safety Issue:
Description:time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive or non invasive]), or death from any cause)
Measure:Event free survival (EFS)
Time Frame:5 years
Safety Issue:
Description:time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive or non invasive]), or death from any cause)
Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:time from randomization to death from any cause
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:time from randomization to death from any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Institut Paoli-Calmettes

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