Clinical Trials /

BreastVax: Radiation Boost to Enhance Effectiveness of Immune Checkpoint Blockade Therapy in Operable Breast Cancer

NCT04454528

Description:

The primary objective is to determine the feasibility of combining pembrolizumab with a single fraction radiation boost in patients with early/operable breast cancer. The secondary objectives are to assess clinical response on pre- and post-treatment clinical, imaging, and histology exams, and to assess immune response on pre and post treatment blood and tissue samples by tracking change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BreastVax: Radiation Boost to Enhance Effectiveness of Immune Checkpoint Blockade Therapy in Operable Breast Cancer
  • Official Title: Preoperative Use of Radiation Boost to Enhance Effectiveness of Immune Checkpoint Blockade Therapy in Operable Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: UPCC 04119
  • NCT ID: NCT04454528

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Pembrolizumab infusionCheckpoint blockade administrationArm 1

Purpose

The primary objective is to determine the feasibility of combining pembrolizumab with a single fraction radiation boost in patients with early/operable breast cancer. The secondary objectives are to assess clinical response on pre- and post-treatment clinical, imaging, and histology exams, and to assess immune response on pre and post treatment blood and tissue samples by tracking change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes.

Detailed Description

      This is a Phase 1b/2 trial employing a Simon Two Stage design to evaluate the safety,
      feasibility, and efficacy (defined as 10% increase in Ki67+ peripheral CD8 T cells
      post-treatment) of a single pembrolizumab infusion with or without radiation boost prior to
      definitive surgery in patients with operable breast cancer. The study has four arms. Arms 1
      and 2 differ by the order of radiation boost and pembrolizumab administration. In arm 3,
      patients will receive pembrolizumab alone. A minimum of 6 patients (3 per arms 1 and 2) will
      be enrolled in the safety run-in portion of the study. An additional 30 patients (9
      additional patients in arms 1 and 2 and up to 12 patients in arm 3) will be enrolled once
      pembrolizumab with the combination radiation is considered feasible and additional funding is
      available. Arm 4 represents our control arm in which patients will follow usual care but will
      be consented for blood/tissue collection using a separate protocol (Penn IRB 801539).
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1Active ComparatorArm 1 will receive radiotherapy on day -14 and pembrolizumab on day -7. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.
  • Pembrolizumab infusion
Arm 2Active ComparatorArm 2 will receive pembrolizumab on day -14 and radiotherapy on day -7. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.
  • Pembrolizumab infusion
Arm 3Active ComparatorArm 3 will receive pembrolizumab on day -14. Subjects in all arms will undergo surgery on day 0 and follow the same postoperative blood sampling and safety schedule.
  • Pembrolizumab infusion
Arm 4OtherArm 4 will not receive any study treatment. Subjects will undergo surgery on day 0 and follow a preoperative (Day 0) and postoperative blood (Day 30) and tissue (Day 0) sampling schedule.

    Eligibility Criteria

            Inclusion Criteria:
    
            All (male and female) subjects must meet the following criteria during screening to be
            enrolled in the study:
    
              1. Is willing and able to provide written informed consent/assent for the trial.
    
              2. A female participant is eligible to participate if she is not pregnant, not
                 breastfeeding, and at least one of the following conditions applies:
    
                   1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 of
                      protocol OR
    
                   2. A WOCBP who agrees to follow the contraceptive guidance during the treatment
                      period and for at least 30 days (corresponding to time needed to eliminate the
                      study drug pembrolizumab plus 30 days [a menstruation cycle] for study treatments
                      with risk of genotoxicity) after the last dose of study treatment.
    
              3. Is 18 years of age on day of signing informed consent.
    
              4. Have an ECOG Performance Status 0 - 1. Evaluation of ECOG is to be performed within 7
                 days prior to the date of allocation/randomization.
    
              5. Patients with newly diagnosed clinical T1-2 N0-1 M0 breast cancer not eligible for
                 I-SPY2 or not undergoing neoadjuvant chemotherapy with at least one of the following
                 features:
    
                   -  Triple negative breast cancer defined using the ASCO CAP guidelines1 with the
                      following modification supported by a recent publication2 as ER ≤ 10%, PR ≤ 10%,
                      and HER2- determined by immunohistochemistry and/or fluorescence in situ
                      hybridization analyses and with tumor size ≤ 2.0 cm, any nodal status and not
                      undergoing neoadjuvant chemotherapy
    
                   -  HR+ HER2- with nodal involvement (node+ disease) confirmed on fine needle
                      aspiration (FNA) or core needle biopsy and clinical T1 or T2 tumor. FNA or core
                      needle biopsy of axilla node are standard diagnostic procedure to confirm nodal
                      involvement.
    
                   -  HR+ or HR- HER2+ breast cancer with clinical T1 tumor (tumor size ≤ 2 cm), any
                      nodal status not undergoing neoadjuvant chemotherapy
    
              6. Locally recurrent breast cancer with no prior radiation expecting surgical excision as
                 part of treatment.
    
              7. Ability to tolerate radiation therapy (e.g., lie flat and hold position).
    
              8. Demonstrate adequate hematologic, renal, hepatic, thyroid and bone marrow function.
                 All screening labs should be performed within 21 days of treatment initiation.
    
              9. 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. Medically
                 accepted methods of birth control include a diaphragm, cervical cap, latex condoms,
                 surgical sterility, intrauterine devices (IUDs), hormonal implants, injectable
                 contraceptives, or birth control pills. Subjects of childbearing potential are those
                 who have not been surgically sterilized or have not been free from menses for > 1
                 year.
    
            Exclusion Criteria:
    
              1. A history of prior radiotherapy that precludes delivery of hypofractionated
                 radiotherapy.
    
              2. Has received prior systemic anti-cancer therapy including investigational agents
                 within 4 weeks [could consider shorter interval for kinase inhibitors or other short
                 half-life drugs] prior to [randomization /allocation].
    
                   -  Note: Participants must have recovered from all AEs due to previous therapies to
                      ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
    
                   -  Note: If participant received major surgery, they must have recovered adequately
                      from the toxicity and/or complications from the intervention prior to starting
                      study treatment.
    
              3. Has a known additional malignancy that is progressing or requires active treatment.
                 Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
                 skin, or in situ cervical cancer that has undergone potentially curative therapy.
    
              4. Has an active autoimmune disease requiring systemic treatment within the past 3 months
                 or a documented history of clinically severe autoimmune disease, or a syndrome that
                 requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
                 resolved childhood asthma/atopy would be an exception to this rule. Subjects that
                 require intermittent use of bronchodilators or local steroid injections would not be
                 excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
                 Sjogren's syndrome will not be excluded from the study. Steroid prep due to dye
                 allergies prior to staging scans or use in anti-emetic prophylaxis is allowed.
    
              5. Has evidence of interstitial lung disease or active, non-infectious pneumonitis or has
                 as a history of (non-infectious) pneumonitis that required steroids or has current
                 pneumonitis.
    
              6. Has an active infection requiring systemic therapy.
    
              7. 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.
    
              8. Has known psychiatric or substance abuse disorders that would interfere with
                 cooperation with the requirements of the trial.
    
              9. 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.
    
             10. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
    
             11. 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.
    
             12. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
    
             13. History of allergy to pembrolizumab.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Feasibility of preoperative pembrolizumab administration combined with radiation boost in patients with operable breast cancer
    Time Frame:2 years
    Safety Issue:
    Description:Feasibility is defined as patient tolerability of the investigational treatment and no excessive delay in surgery in our participants. The interval to breast-conserving surgery and mastectomy was based on review of our records in patients undergoing breast cancer surgery in 2016. The average time to breast conservation surgery is 24.3 days (80% between 9 and 51 days) and for mastectomy with reconstruction 41.6 days (80% between 10 and 67 days).

    Secondary Outcome Measures

    Measure:Assess immune response on pre- and post-treatment blood and tissue samples
    Time Frame:2 years
    Safety Issue:
    Description:This study will track change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes (TIL).

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:University of Pennsylvania

    Trial Keywords

    • Immune checkpoint blockade

    Last Updated

    June 29, 2020