Phase II PEMBROLIZUMAB + PALLIATIVE RADIOTHERAPY IN BC
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pembrolizumab; Palliative radiotherapy
Intervention description: Pembrolizumab (formerly MK-3475) is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD1 and its ligands, PD-L1 and PD-L2.; Palliative radiotherapy aims to shrink cancer, slow down its growth or control symptoms.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

Summary:

      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
    

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
             screening

          -  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
             have:

               -  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
             pneumonitis.

          -  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
             Pembrolizumab.

          -  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