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This research study is studying radiation therapy in combination with an immunotherapy as a possible treatment for metastatic hormone receptor (HR) positive, HER2-negative breast cancer. The interventions involved in this study are: - Palliative Radiotherapy - Pembrolizumab

Related Conditions:
  • Breast Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Official Title: A Phase II Study Of Pembrolizumab In Combination With Palliative Radiotherapy For Metastatic Hormone Receptor Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 16-588
  • NCT ID: NCT03051672


  • Metastatic Breast Cancer


PembrolizumabKeytrudaPembrolizumab With Radiation


This research study is studying radiation therapy in combination with an immunotherapy as a possible treatment for metastatic hormone receptor (HR) positive, HER2-negative breast cancer. The interventions involved in this study are: - Palliative Radiotherapy - Pembrolizumab

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. "Investigational" means that the intervention is being

      In this research study, the investigators are evaluating the safety and effectiveness of
      palliative radiotherapy ("radiation therapy") in combination with pembrolizumab in
      HR-positive, HER2-negative breast cancer. This study is designed to test how well radiation
      therapy in combination with pembrolizumab treats this type of cancer.

      The FDA has approved radiation therapy as a treatment option for this type of breast cancer.

      The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this
      specific disease but it has been approved in the United Sates for other types of cancer.

      Pembrolizumab is a drug that may treat cancer by working with the immune system. The immune
      system is the body's natural defense against disease. The immune system sends types of cells
      called "T cells" throughout the body to detect and fight infections and diseases, including
      cancer. For some types of cancer, the T cells do not work as they should and are prevented
      from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the T
      cells called PD-1 ("programmed death 1"), which then allows these cells and other parts of
      the immune system to attack tumors.

      The combination of pembrolizumab and radiation therapy is investigational. The study drug and
      radiation therapy, when given separately, work in different waysto help stop the cancer cells
      from growing and spreading. However, it is not known if giving the study drug and radiation
      therapy at the same time will have a better anti-cancer effect than giving each treatment on
      its own.

Trial Arms

Pembrolizumab With RadiationExperimentalPembrolizumab will be administered intravenously prior to radiation Pembrolizumab will be administered every 21 days Palliative radiotherapy will be given for 5 treatments
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically or cytologically confirmed invasive breast
             cancer, with metastatic disease. Participants without pathologic or cytologic
             confirmation of metastatic disease should have unequivocal evidence of metastasis from
             physical examination or radiologic evaluation.

          -  Invasive disease must have been tested for ER, PR and HER2. Participants must have
             hormone-receptor positive, HER2-negative breast cancer defined as:

               -  ER>1% or PR>1%

               -  HER2-negative per ASCO CAP guidelines, 2013 [Wolff et al., 2013]

          -  Participant must be a candidate for palliative radiation treatment to at least one
             bone, lymph node, or soft tissue lesion. Radiation of visceral lesions (such as lung
             or hepatic lesions) is not permitted.

          -  Participant must have measurable disease outside the field of radiation as defined by
             RECIST 1.1.

          -  If tumor is accessible and outside the field of radiation, the participant must be
             willing to undergo a research biopsy at baseline and after 2 cycles of pembrolizumab.
             Participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or
             safety concern) must be willing to submit an archival specimen.

          -  Prior systemic therapy:

               -  Participant must be at least 14 days from the last dose of prior chemotherapy,
                  endocrine therapy, biological agents (including small molecule targeted therapy)
                  or any investigational drug product with adequate recovery of toxicity to
                  baseline, or grade 1(with the exception of alopecia and hot flashes) at the time
                  of registration.

               -  There is no limit to the number of prior lines of therapy, including endocrine or
                  cytotoxic agents. Systemic treatment naive patients for metastatic disease are
                  also eligible.

               -  Participants may initiate or continue bisphosphonate therapy on study.

               -  Continuation of ovarian suppression is allowed.

          -  Prior radiation therapy:

               -  Patients must be at least 3 months from prior radiation therapy

               -  Re-irradiation of the same field is not allowed

          -  Concurrent administration of other cancer specific therapy during the course of this
             study is not allowed.

          -  The subject is ≥18 years old

          -  ECOG performance status ≤1 (See Appendix A for details)

          -  Participants must have normal organ and marrow function as defined below:

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  hemoglobin ≥ 8 g/dl

               -  total bilirubin ≤1.5 × institutional upper limit of normal (ULN)

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or ≤ 5 × institutional ULN for
                  participants with documented liver metastases

               -  creatinine ≤1.5 ×within normal institutional ULN (or 2.0 x ULN in patients with
                  documented Gilbert's Syndrome) OR creatinine clearance ≥60 mL/min/1.73 m2 for
                  participants with creatinine levels above institutional ULN.

               -  International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the
                  upper limit of normal 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 times the upper limit of normal
                  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 must have a negative pregnancy test at

          -  Female and male subjects of childbearing potential must agree to use an adequate
             method of contraception as outlined in section 5.4.1. Contraception is required
             starting with the first dose of study medication through 120 days after the last dose
             of study medication Note: Abstinence is acceptable if this is the usual lifestyle and
             preferred contraception for the subject.

          -  Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1
             severity or lower, except for stable sensory neuropathy (≤ Grade 2) and alopecia.

          -  The subject is capable of understanding and complying with the protocol and has signed
             the informed consent document

        Exclusion Criteria:

          -  Participants who are receiving any other investigational agents.

          -  Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to pembrolizumab.

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms. Participants with previously diagnosed brain metastases are eligible if they

               -  completed treatment (whole brain radiotherapy, radiosurgery, or a combination) at
                  least 3 months prior to trial therapy initiation,

               -  are neurologically stable, and

               -  have recovered from effects of radiotherapy or surgery. Any corticosteroid use
                  for brain metastases must have been discontinued without the subsequent
                  appearance of symptoms for ≥2 weeks before prior to registration.

          -  Radiologic or clinical evidence of Spinal Cord Compression.

          -  Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a neurosurgical
             service and considered stable.

          -  Participants with bone lesions requiring surgical fixation to provide mechanical
             stability are ineligible. Participants with previously fixed lesions are allowed.

          -  The participant has an uncontrolled intercurrent illness, including, but not limited
             to uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac
             arrhythmia, congestive heart failure-New York Heart Association Class III or IV,
             active ischemic heart disease, myocardial infarction within the previous six months,
             uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the
             previous 6 months, severe malnutrition or psychiatric illness/social situations that
             would limit compliance with study requirements.

          -  Clinically significant electrocardiogram (ECG) abnormality, including a marked
             baseline prolonged QT/QTc ([QT interval/corrected QT interval], eg, a repeated
             demonstration of a QTc interval >500 ms).

          -  Participant has a medical condition that requires chronic systemic steroid therapy or
             on any other form of immunosuppressive medication. For example, patients with
             autoimmune disease that requires systemic steroids or immunosuppression agents should
             be excluded. 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 history of (non-infectious) pneumonitis that required steroids or current

          -  Has a history of interstitial lung disease.

          -  The participant is known to be positive for the human immunodeficiency virus (HIV),
             HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy
             are ineligible because of the potential for pharmacokinetic interactions with

          -  Individuals with a history of different malignancy are ineligible except for the
             following circumstances. Individuals with a history of other malignancies are eligible
             if they have been disease-free for at least 3 years or are deemed by the investigator
             to be at low risk for recurrence of that malignancy.

          -  Has received a live vaccine within 30 days of planned start of study therapy.

          -  The participant is pregnant or breast-feeding
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:

Secondary Outcome Measures

Measure:Immune Response Rate
Time Frame:2 years
Safety Issue:
Measure:Clinical Benefit Response Rate
Time Frame:2 years
Safety Issue:
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Measure:Absolute Risk Reduction
Time Frame:2 years
Safety Issue:


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer

Last Updated

April 1, 2019