Clinical Trials /

Pembrolizumab in High-risk Ductal Carcinoma in Situ (DCIS)

NCT02872025

Description:

This is a pilot study to investigate the change in the immune microenvironment of high risk ductal carcinoma in situ (DCIS) after short term exposure to pembrolizumab.

Related Conditions:
  • Ductal Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in High-risk Ductal Carcinoma in Situ (DCIS)
  • Official Title: Testing the Ability of Pembrolizumab to Alter the Tumor Immune MicroEnvironment (TIME) of High Risk DCIS

Clinical Trial IDs

  • ORG STUDY ID: 16704
  • NCT ID: NCT02872025

Conditions

  • Carcinoma, Intraductal, Noninfiltrating

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475Pembrolizumab intralesionally (IL) x 2 doses

Purpose

This is a pilot study to investigate the change in the immune microenvironment of high risk ductal carcinoma in situ (DCIS) after short term exposure to pembrolizumab.

Detailed Description

      This study will include 3 dose cohorts using a 3+3 cohort dose escalation design (see figure
      1) followed by a 4th cohort at the maximum tolerated dose. Unless a dose limiting toxicity
      (DLT), defined any grade 3 or 4 toxicity, is observed requiring expansion of a cohort or a
      subject withdraws, 3 subjects will be enrolled into each cohort in the dose escalation phase.
      Subjects, upon diagnosis with high risk DCIS, will be offered 2 doses of pembrolizumab
      injected intralesionally (IL) 3 weeks apart (+/- 1 week) with surgery 3 weeks (+/- 2 weeks)
      after the 2nd dose. The subject will then undergo the surgical treatment as determined by the
      surgeon and the subject (partial mastectomy or mastectomy). The primary objective of this
      phase of the study will be safety and feasibility of intralesional injection of
      pembrolizumab. The maximum tolerated dose will be used in the expansion phase. The expansion
      cohort will have a target enrollment of 30 subjects randomized to either the control group or
      the treatment group. 10 subjects will be randomized to the control group and 20 subjects will
      be randomized to the treatment group. The control group will proceed to surgery alone
      following the diagnosis of high risk DCIS. The treatment group will receive 2 doses of
      intralesional pembrolizumab 3 weeks apart (+/- 1 week) prior to surgery. All subjects in the
      expansion cohort will also undergo a baseline MRI at diagnosis and undergo a 2nd MRI prior to
      surgery. Baseline and pre-surgical MRI images will be evaluated for changes in tumor volume.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab intralesionally (IL) x 2 dosesExperimentalSubjects, upon diagnosis with high risk DCIS, will be offered 2 doses of pembrolizumab injected intralesionally (IL) 3 weeks apart (+/- 1 week) with surgery 3 weeks (+/- 2 weeks) after the 2nd dose. The subject will then undergo the surgical treatment as determined by the surgeon and the subject (partial mastectomy or mastectomy).
  • Pembrolizumab
No active treatmentNo InterventionThe control group will proceed to surgery alone following the diagnosis of high risk DCIS.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Plan on having surgical treatment to remove the lesion
    
              -  Have at least 2 of the following high risk features associated with her DCIS -
                 high-grade (grade II-III), palpable mass, hormone receptor negative (less than 1%),
                 Her2 positive, young age (less than 45 years old), and large size (greater than 5 cm)
    
              -  Patients with a history of tamoxifen and/or aromatase inhibitor use for treatment or
                 prevention are eligible but should discontinue these medications at least 2 weeks
                 prior to starting this trial
    
              -  Be willing and able to provide written informed consent/assent for the trial.
    
              -  Be >=18 years of age on day of signing informed consent.
    
              -  Have a performance status of 0 or 1 on the ECOG Performance Scale.
    
              -  Demonstrate adequate organ function as defined in Table 1 Adequate Organ Function
                 Laboratory Values
    
              -  All screening labs should be performed within 10 days of treatment initiation.
    
              -  Hematological Absolute Neutrophil Count (ANC) >=1,500/mcL Platelets >=100,000/mcL
                 Hemoglobin >=9 g/dL or >=5.6 mmol/L without transfusion or EPO dependency (within 7
                 days of assessment)
    
              -  Renal Serum creatinine <=1.5 X upper limit of normal (ULN) OR Measured or calculated
                 creatinine clearance (GFR can also be used in place of creatinine or CrCl) >=60 mL/min
                 for subject with creatinine levels > 1.5 X institutional ULN
    
              -  Hepatic Serum total bilirubin <=1.5 xULN OR Direct bilirubin <= ULN for subjects with
                 total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) <= 2.5 X ULN Albumin
                 >=2.5mg/dL
    
              -  Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) <=1.5 X ULN
                 unless subject is receiving anticoagulant therapy as long as PT or PTT is within
                 therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin
                 Time (aPTT) <=1.5 X ULN unless subject is receiving anticoagulant therapy as long as
                 PT or PTT is within therapeutic range of intended use of anticoagulants
    
              -  Female subjects of childbearing potential should have a negative urine or serum
                 pregnancy 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.
    
              -  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 (Reference
                 Section 5.7.2). Subjects of childbearing potential are those who have not been
                 surgically sterilized or have not been free from menses for > 1 year.
    
            Exclusion Criteria:
    
              -  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.
    
              -  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.
    
              -  Is not interested in surgical treatment of her DCIS
    
              -  Has invasive breast cancer
    
              -  Has a known history of active TB (Bacillus Tuberculosis)
    
              -  Hypersensitivity to pembrolizumab or any of its excipients.
    
              -  Has a known additional malignancy that is progressing or requires active treatment.
                 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.
    
              -  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 (e.g.,, thyroxine, insulin, or physiologic corticosteroid
                 replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
                 form of systemic treatment.
    
              -  Has history of/active pneumonitis that required/is requiring steroid treatment or had
                 history of/active interstitial lung disease. Has an active infection requiring
                 systemic therapy.
    
              -  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.
    
              -  Has known psychiatric or substance abuse disorders that would interfere with
                 cooperation with the requirements of the trial.
    
              -  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.
    
              -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
    
              -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    
              -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
                 [qualitative] is detected).
    
              -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
                 Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
                 are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
                 attenuated vaccines, and are not allowed.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Maximum tolerated dose (MTD)
    Time Frame:18 months
    Safety Issue:
    Description:To determine the maximum tolerated dose (MTD), and recommended dose for subsequent expansion cohort, of intralesionally administered pembrolizumab in patients with ductal carcinoma in situ (DCIS) of the breast.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Laura Esserman

    Last Updated

    October 24, 2017