Clinical Trials /

Converting HR+ Breast Cancer Into an Individualized Vaccine

NCT03804944

Description:

Newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer are eligible to a randomized trial, concurrently open at five US academic institutions. Patients receiving 4 months of standard neoadjuvant hormonal therapy with letrozole are randomly assigned to one of 4 arms of a trial testing focal hypo-fractionated RT alone or with immunotherapy combinations.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Converting HR+ Breast Cancer Into an Individualized Vaccine
  • Official Title: Converting HR+ Breast Cancer Into an Individualized Vaccine

Clinical Trial IDs

  • ORG STUDY ID: 1808019498
  • NCT ID: NCT03804944

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Pembrolizumab (200mg IV for 30 minutesARM 2
CDX-301ARM 3

Purpose

Newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer are eligible to a randomized trial, concurrently open at five US academic institutions. Patients receiving 4 months of standard neoadjuvant hormonal therapy with letrozole are randomly assigned to one of 4 arms of a trial testing focal hypo-fractionated RT alone or with immunotherapy combinations.

Detailed Description

      Patients will be on the study for a total of 5 months, this includes 4 months on active study
      intervention, with breast surgery at week 16 and one month follow up period, after surgery.
      Patients will be randomly assigned to one of these 4 arms - 1. Anti-PD1 antibody
      pembrolizumab (Keytruda, Merck) will be infused day 12, at the standard dose of 200 mg IV
      over 30 minutes, repeated every 3 weeks until disease progression or unacceptable toxicity.
      2. FLT3L (CDX-301, the recombinant human protein by Celldex) will be self-administered
      subcutaneously, in 5 consecutive daily injections, week 1, day 1-5. 3. For all arms radiation
      therapy to the breast tumor will begin on week 2 (Day 8,10,12), at dose of 8 Gy x 3
      fractions, every other day. 4. Letrozole (Femara ®, Novartis) 2.5 mg tabs, once a day, daily
      for 4 months, until surgery, and thereafter is decided by the treating physician.
    

Trial Arms

NameTypeDescriptionInterventions
ARM 1Active ComparatorFocal hypo-fractionated radiation therapy 8 Gy x 3 fractions, starting day 8, every other day (M/W/F or W/F/M or F/M/W).
    ARM 2Active ComparatorFocal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), infused over 200mg IV over 30 minutes and then repeated every 3 weeks until disease progression or unacceptable toxicity.
    • Pembrolizumab (200mg IV for 30 minutes
    ARM 3Active ComparatorFtl-3 ligand, self-administered by subcutaneous injections at week 1, daily, for 5 consecutive days + Focal hypo-fractionated radiation therapy - 8 Gy x 3 fractions starting day 8, (every other day (M/W/F or W/F/M or F/M/W).
    • CDX-301
    ARM 4Active ComparatorFtl-3 ligand, self administered subcutaneous injections at day 1 for 5 consecutive days+ Focal hypo-fractionated Radiation therapy starting day 8, - 8 Gy x 3 fractions, every other day (M/W/F or W/F/M or F/M/W). + Pembrolizumab, on day 12 (last day of radiotherapy), 200mg IV infused over 30 minutes then repeated every 3 weeks until disease progression or unacceptable toxicity.
    • Pembrolizumab (200mg IV for 30 minutes
    • CDX-301

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Post-menopausal female ≥ 18 years of age (Post-menopausal status defined as either 1)
                 at least 2 years without menstrual period or 2) or patients older than 50 with
                 serological evidence of post-menopausal status or 3) hysterectomized patients of any
                 age with FSH confirmation of post-menopausal status.
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    
              -  Biopsy proven diagnosis of ER+HER2- breast cancer.
    
              -  Patient needs to be able to understand and demonstrate willingness to sign a written
                 informed consent document.
    
            Adequate bone marrow reserve and liver function:
    
            WBC ≥ 2000/uL Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100 000/μL Hemoglobin
            ≥9.0 g/dL or ≥5.6 mmol/La Creatinine OR Measured or calculated creatinine clearance (GFR
            can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant
            with creatinine levels >1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN OR direct
            bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT
            (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International
            normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time
            (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or
            aPTT is within therapeutic range of intended use of anticoagulants
    
            Exclusion Criteria:
    
              -  Active connective tissue disorders, such as lupus or scleroderma requiring flare
                 therapy
    
              -  Current use of systemic chemotherapy, endoctine therap or HER2-neu targeted therapy
    
              -  Pre menopausal patients.
    
              -  Male breast cancer patients
    
              -  Post surgical excision of breast cancer.
    
              -  Previous radiotherapy of the same breast.
    
              -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
                 an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
                 OX-40, CD137).
    
              -  Inability to obtain histologic proof of breast cancer
    
              -  Has received a live vaccine within 30 days prior to the first dose of study drug.
    
            Examples of live vaccines include, but are not limited to, the following: measles, mumps,
            rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin
            (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
            virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are
            live attenuated vaccines and are not allowed.
    
              -  Is currently participating in or has participated in a study of an investigational
                 agent or has used an investigational device within 4 weeks prior to the first dose of
                 study treatment. Note: Participants who have entered the follow-up phase of an
                 investigational study may participate as long as it has been 4 weeks after the last
                 dose of the previous investigational agent.
    
              -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
                 (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
                 immunosuppressive therapy within 7 days prior to the first dose of study drug.
    
              -  Has a known additional malignancy (second primary) that is progressing or has required
                 active treatment within the past 3 years. Note: Participants with basal cell carcinoma
                 of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical
                 cancer in situ) that have undergone potentially curative therapy are not excluded.
    
              -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
    
              -  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.
    
              -  Has a history of (non-infectious) pneumonitis that required steroids or has current
                 pneumonitis.
    
              -  Has an active infection requiring systemic therapy.Has a known history of Human
                 Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by
                 local health authority.
    
              -  Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
                 reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
                 detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
                 unless mandated by local health authority.
    
              -  Has a known history of active TB (Bacillus Tuberculosis). Note: optional based on
                 country.
    
              -  Has known psychiatric or substance abuse disorders that would interfere with
                 cooperation with the requirements of the trial.
          
    Maximum Eligible Age:90 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Tolerability will be demonstrated if no grade 3 or higher toxicities are observed in the first 8 patients, of each arm.
    Time Frame:3 years
    Safety Issue:
    Description:Tolerability of adding immunotherapy to a combination of tumor radiotherapy and endocrine therapy in the neoadjuvant setting of newly diagnosed HR+ breast cancer patients will be assessed if no grade 3 or higher toxicities are observed in the first 8 patients of each arm. CTCAE version 5.0 will be used.

    Secondary Outcome Measures

    Measure:Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.
    Time Frame:4 years
    Safety Issue:
    Description:Local immune response will be measured by assessing tumor specimens for T-cell infiltration at baseline and and during treatment.
    Measure:Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.
    Time Frame:4 years
    Safety Issue:
    Description:Systemic immune response will be measured by collecting serial blood samples for serum and peripheral blood mononuclear cells (PBMCs) at multiple time points.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Weill Medical College of Cornell University

    Last Updated