Clinical Trials /

Breast Cancer Study of Preoperative Pembrolizumab + Radiation

NCT03366844

Description:

This study is being done to assess the safety and tolerability of pembrolizumab (study drug) combined with standard radiation to the tumor (tumor boost) before patients undergo standard treatment that can consist of one or more of the following: breast-conserving surgery, radiation to the entire breast/chest wall after surgery, and chemotherapy. Study participants will receive two doses of the study drug intravenously (through the vein) before their planned breast surgery or chemotherapy. The study drug will be administered three weeks apart. At the time of the second dose, radiation to the tumor in the affected breast will be given. This type of radiation treatment is called a "tumor boost", which is a standard part of radiation therapy for breast cancer that may occur either before or after planned breast-conserving surgery. Patients will receive breast surgery or begin chemotherapy approximately six weeks after your first dose of the study drug.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot; Open Label; Breast Cancer; Preoperative Pembrolizumab + Radiation
  • Official Title: Pilot Study of the Preoperative Combination of Pembrolizumab and Radiation Therapy in Patients With Operable Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: IIT2017-07-HO-PembroRT
  • NCT ID: NCT03366844

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, MK-3475Pembrolizumab with RT Boost

Purpose

This study is being done to assess the safety and tolerability of pembrolizumab (study drug) combined with standard radiation to the tumor (tumor boost) before patients undergo standard treatment that can consist of one or more of the following: breast-conserving surgery, radiation to the entire breast/chest wall after surgery, and chemotherapy. Study participants will receive two doses of the study drug intravenously (through the vein) before their planned breast surgery or chemotherapy. The study drug will be administered three weeks apart. At the time of the second dose, radiation to the tumor in the affected breast will be given. This type of radiation treatment is called a "tumor boost", which is a standard part of radiation therapy for breast cancer that may occur either before or after planned breast-conserving surgery. Patients will receive breast surgery or begin chemotherapy approximately six weeks after your first dose of the study drug.

Detailed Description

      With more than 1 million new cases diagnosed yearly worldwide, breast cancer is a global
      public health burden. Over the past decade, molecular subtyping of breast cancer has
      identified intrinsic subtypes that may be at enhanced risk for both local and distant
      recurrence. This study focuses on the immunogenicity of high-risk breast cancer subtypes that
      are likely to display a dense lymphocytic infiltration including including TNBC and HR+/HER2-
      tumors.

      Immune build up via immune co-stimulatory molecules permits the ensuing immune response to
      strengthen and destroy cancer systemically. Thus, the effect of the anti-tumor immune
      response initiated by the radiation to an intact tumor by combination with checkpoint
      blockade is increased.

      Pembrolizumab is an optimal immunotherapy agent to study, as this agent has recently been FDA
      approved for use in multiple tumor types. It is therefore ready to be tested for efficacy in
      other disease sites and in combination with other treatments.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab with RT BoostExperimentalStudy drug plus "tumor boost" before standard of care treatment
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed histologic diagnosis of invasive adenocarcinoma of the breast, and

          -  ER, PR and HER2 testing (on outside or Cedars-Sinai biopsy report), and

               -  High-risk, ER-positive and HER2-negative breast cancer patients. ER-positive
                  disease is defined as ER>10%, any PR and HER2-negative by ASCO CAP guidelines.
                  High-risk disease will be defined by the presence of at least 2 of the following
                  3 criteria: histologic grade II-III, Ki-67 > 20%, ER expression < 75% by IHC)

               -  TNBC patients (defined as ER<1%, PR1%, HER2-neu 0-1+ by IHC or FISH-negative; or
                  as per MD discretion)

          -  Operable tumor measuring ≥2 cm in maximal diameter as measured by any available
             standard of care imaging (mammogram, breast ultrasound, breast MRI)

          -  Any nodal status

          -  Multifocal disease is permitted; largest focus must measure ≥2 cm

          -  Synchronous bilateral invasive breast cancer is permitted

          -  No indication of distant metastases

          -  Breast-conserving therapy is planned

          -  Tumor amenable to preoperative radiation therapy boost as determined by radiation
             oncologist

          -  ECOG performance status score of 0 or 1

          -  Screening laboratory values must meet the following criteria:

             i. White blood cells (WBCs) ≥ 2000/μL ii. Absolute neutrophil count (ANC) ≥ 1500/μL
             iii. Platelets ≥ 100 x 103/μL iv. Hemoglobin ≥ 11.0 g/dL v. Serum creatinine ≤ 2 mg/dL
             (or glomerular filtration rate ≥ 40 ml/min) vi. AST ≤ 2.5 x upper limit of normal
             (ULN) vii. ALT ≤ 2.5 x ULN viii. Bilirubin within normal limits (except subjects with
             Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL) ix. Negative HIV
             screening test x. Negative screening tests for Hepatitis B and Hepatitis C. Patients
             with positive results that do not indicate true active or chronic infection may enroll
             after discussion and consensus agreement by the treating physician and principal
             investigator.

          -  Women of childbearing potential (WOCBP) must be using an acceptable method of
             contraception to avoid pregnancy throughout the study and for at least 4 months after
             the last dose of pembrolizumab in such a manner that the risk of pregnancy is
             minimized. See below for the definition of WOCBP.

          -  WOCBP must have a negative serum pregnancy test within 14 days prior to the first dose
             of pembrolizumab.

          -  Women must not be breastfeeding.

          -  Willingness to adhere to the study visit schedule and the prohibitions and
             restrictions specified in this protocol.

          -  Willingness to undergo mandatory Week 4 research biopsy

          -  Written informed consent obtained from subject and ability for subject to comply with
             the requirements of the study.

        Exclusion Criteria:

          -  HER2-positive breast cancer defined as IHC3+ or IHC2+ with FISH>2 AND copy number >4
             OR FISH <2 AND copy number >6

          -  Inflammatory breast cancer

          -  Contraindication(s) to breast-conserving therapy

          -  Contraindication to radiation therapy or planned partial breast irradiation

          -  Patients with cosmetic breast augmentations at the time of diagnosis

          -  Medical history and concurrent diseases

               -  Subjects with active, known or suspected autoimmune disease. Subjects with
                  vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
                  condition only requiring hormone replacement, psoriasis not requiring systemic
                  treatment, or conditions not expected to recur in the absence of an external
                  trigger are permitted to enroll.

               -  Any serious or uncontrolled medical disorder that, in the opinion of the
                  investigator, may increase the risk associated with study participation or study
                  drug administration, impair the ability of the subject to receive protocol
                  therapy, or interfere with the interpretation of study results.

               -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

               -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
                  [qualitative] is detected).

          -  Prohibited Treatments and/or Therapies

               -  Chronic use of immunosuppressants and/or systemic corticosteroids (used in the
                  management of cancer or non-cancer-related illnesses). However, use of
                  corticosteroids is allowed for the treatment of immune related Adverse Events
                  (irAEs), or adrenal insufficiency.

               -  Any non-oncology vaccine therapy used for prevention of infectious diseases
                  within 4 weeks prior to first dose of pembrolizumab.

               -  Prior treatment with pembrolizumab or other PD-1/PD-L1 inhibitor.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients who do not necessitate a delay in standard of care treatment after receiving the investigational combination of preoperative Pembrolizumab and radiation
Time Frame:8 weeks after trial initiation
Safety Issue:
Description:Safety/tolerability of preoperative radiation and Pembrolizumab in newly diagnosed, non-metastatic patients with triple negative breast cancer.

Secondary Outcome Measures

Measure:Pembrolizumab-related adverse events
Time Frame:15 weeks after trial initiation
Safety Issue:
Description:Treatment toxicities
Measure:Immune-related adverse events
Time Frame:15 weeks after trial initiation
Safety Issue:
Description:Treatment toxicities
Measure:Invasive disease-free survival after preoperative radiation and Pembrolizumab
Time Frame:From treatment start date until date of documented recurrence or death from breast cancer, assessed up to 19 weeks after start of treatment
Safety Issue:
Description:Disease-free survival, as described from time from occurrence of surgery to time from first recurrence from or death from breast cancer

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alice Ho

Trial Keywords

  • invasive adenocarcinoma of the breast
  • ER-positive and HER2-negative breast cancer
  • Triple negative breast cancer (TNBC)
  • immunotherapy
  • checkpoint inhibitor

Last Updated

December 4, 2017