Clinical Trials /

Atezolizumab + Stereotactic Radiation in Triple-negative Breast Cancer and Brain Metastasis

NCT03483012

Description:

This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible treatment for triple-negative breast cancer that has spread to the brain. The interventions involved in this study are: - Atezolizumab - Stereotactic radiosurgery (SRS)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab + Stereotactic Radiosurgery in Triple-negative Breast Cancer and Brain Metastasis
  • Official Title: A Phase II Study of Atezolizumab in Combination With Stereotactic Radiosurgery for Patients With Triple-negative Breast Cancer and Brain Metastasis

Clinical Trial IDs

  • ORG STUDY ID: 17-519
  • NCT ID: NCT03483012

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab + Stereotactic radiosurgery (SRS)

Purpose

This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible treatment for triple-negative breast cancer that has spread to the brain. The interventions involved in this study are: - Atezolizumab - Stereotactic radiosurgery (SRS)

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
      studied.

      The FDA (the U.S. Food and Drug Administration) has not approved atezolizumab for this
      specific disease but it has been approved for other uses.

      Atezolizumab is a protein that affects the immune system by blocking the PD-L1 pathway. The
      PD-L1 pathway controls the body's natural immune response, but tumors can interrupt this
      pathway and partially resist or escape the immune system. By blocking the PD-L1 pathway,
      Atezolizumab may help the immune system identify and catch tumor cells.

      Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in
      the brain. SRS uses many precisely focused radiation beams to treat tumors. It is not surgery
      in the traditional sense because there's no incision. Instead, SRS uses 3-D imaging to target
      high doses of radiation to the affected area with minimal impact on the surrounding healthy
      tissue. Like other forms of radiation, SRS works by damaging the DNA of the targeted (tumor)
      cells. The affected cells then lose the ability to reproduce, which causes tumors to shrink.

      When given separately, atezolizumab and SRS, work in different ways to help stop cancer cells
      from growing and spreading. However, it is not known if giving atezolizumab and SRS at the
      same time will have a better effect than giving each treatment on its own. It is hoped that
      SRS treatment will damage cancer cells and make them more visible to the immune system.

      The researchers conducting this study are testing to see whether giving SRS with atezolizumab
      may boost the body's immune response to cancer, and therefore improve upon the effects of
      either SRS or atezolizumab given alone.

      In this research study, the investigators will measure the length of time that the
      participant receive this study intervention without the disease getting worse. The
      investigators will also look at how well the disease responds to atezolizumab and SRS as well
      as the safety of the combination.
    

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab + Stereotactic radiosurgery (SRS)ExperimentalAtezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

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

          -  Either the primary tumor and/or metastatic tumor must be triple-negative as defined
             below:

               -  Hormone receptor status: the invasive tumor must be ER- and PR-negative, or
                  staining present in <1% by immunohistochemistry (IHC)

               -  HER2 status: the invasive tumor must be Human Epidermal Growth Factor Receptor 2
                  Negative (HER2-negative) by the ASCO CAP guidelines

          -  In cases where both primary tumor and metastatic sample(s) have been tested for ER,
             PR, and HER2, the triple-negative status of the most recent sample should be used.

          -  Participants must have a diagnosis of brain metastases for which SRS is indicated, as
             determined by a radiation oncologist.

          -  The contrast-enhancing intraparenchymal brain metastases(s) must be well circumscribed
             and must have a maximum diameter of ≤ 3.0 cm in any direction on the enhanced scan.

          -  Participants must not have more than 5 new or progressive lesions in the brain
             requiring SRS treatment (greater than 5 total brain lesions are allowed as long as no
             more than 5 lesions require SRS treatment).

          -  Participants must have measurable extracranial disease as defined by RECIST 1.1.

          -  Participants must be willing to undergo a research biopsy at baseline and at Cycle 2
             Day 1 if extracranial metastases are safely accessible. Participants for whom biopsies
             cannot be safely performed must be willing to submit an archival primary and/or
             metastatic specimen. The biopsies may be waived with prior PI approval for the first 6
             participants enrolled to the safety run in phase.

          -  Prior systemic therapy:

               -  Participants must have discontinued systemic therapy at least 14 days prior to
                  initiating protocol therapy.

               -  There is no limit to the number of prior lines of systemic therapy. Participants
                  who have not received any systemic therapy for metastatic disease are also
                  eligible.

               -  Participants may initiate or continue bisphosphonate therapy on study.

          -  Prior local therapy:

          -  Prior surgery, whole brain radiation or SRS is allowed as long as the most recent
             brain progression is amenable to SRS treatment.

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

          -  Participant is ≥18 years old.

          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

          -  Stable dose of dexamethasone 2mg or less for at least 7 days prior to initiation of
             treatment

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

               -  absolute neutrophil count ≥1,000/μl

               -  platelets ≥75,000/μl

               -  hemoglobin ≥9 g/dL

               -  total bilirubin ≤1.5mg/dL (≤2.0 in patients with known Gilberts syndrome)

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. ≤5.0 × institutional ULN for
                  patients with documented liver metastases.

               -  albumin >2.5mg/dL

               -  serum creatinine ≤1.5mg/dL or calculated GFR ≥60 mL/min

          -  Female subjects of childbearing potential must have a negative serum or urine
             pregnancy test within 8 days of initiating protocol therapy.

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of < 1% per year during the treatment period and for at least 90 days after the last
             dose of study treatment. A woman is considered to be of childbearing potential if she
             is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of
             amenorrhea with no identified cause other than menopause), and has not undergone
             surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive
             methods with a failure rate of < 1% per year include bilateral tubal ligation, male
             sterilization, established, proper use of hormonal contraceptives that inhibit
             ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
             The reliability of sexual abstinence should be evaluated in relation to the duration
             of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
             withdrawal are not acceptable methods of contraception. The effects of atezolizumab on
             the developing human fetus are unknown and radiotherapy has known teratogenic effects
             so women of child-bearing potential and men must agree to use adequate contraception
             (barrier method of birth control; abstinence) prior to study entry and for the
             duration of study participation and 4 months after completion of atezolizumab
             administration.

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

        Exclusion Criteria:

          -  CNS complications for whom urgent neurosurgical intervention is indicated (e.g.,
             resection, shunt placement).

          -  Known leptomeningeal or brainstem metastases. The presence of leptomeningeal
             enhancement alone, without associated clinical manifestations and/or positive CSF
             cytology, will not be constituted as known leptomeningeal metastases.

          -  Treatment with high dose systemic corticosteroids defined as dexamethasone >2mg/day or
             bioequivalent within 7 days of initiating therapy.

          -  Patients unable to undergo gadolinium contrast-enhanced MRI or receive IV contrast for
             any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme
             obesity, hypersensitity).

          -  Participants who are receiving any other investigational agents.

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

          -  Subjects with a history of hypersensitivity to compounds of similar biologic
             composition to atezolizumab or any constituent of the product

          -  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.

          -  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 evidence of active, noninfectious pneumonitis that requires treatment with
             steroids.

          -  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
             atezolizumab.

          -  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 principal
             investigator to be at low risk for recurrence of that malignancy.

          -  Has received a live vaccine within 28 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:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:24 weeks
Safety Issue:
Description:Assessed using RANO-BM criteria

Secondary Outcome Measures

Measure:Extracranial Objective Response Rate
Time Frame:24 weeks
Safety Issue:
Description:Assessed by RECIST 1.1
Measure:Extracranial Objective Response Rate
Time Frame:24 weeks
Safety Issue:
Description:Assessed by immune-related response criteria (irRC)
Measure:Progression free survival
Time Frame:24 weeks
Safety Issue:
Description:Assessed by RECIST 1.1
Measure:Clinical Benefit Rate
Time Frame:16 and 24 weeks
Safety Issue:
Description:defined as CR, PR and stable disease
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:evaluate the overall survival (OS) of atezolizumab in combination with SRS in patients with TNBC and brain metastasis
Measure:Patient-Reported Outcome
Time Frame:2 years
Safety Issue:
Description:Evaluated by MDASI-BT assessment.
Measure:Development of radiation necrosis
Time Frame:2 years
Safety Issue:
Description:Assessed by neuroradiology assessment or dual-phase PET-CT studies
Measure:Investigator-Assessed Neurological Evaluation
Time Frame:2 years
Safety Issue:
Description:Evaluated by physician assessed Neurological Assessment in Neuro-Oncology (NANO) scale
Measure:Dose Limiting Toxicity
Time Frame:First dose of atezolizumab until Cycle 3 Day 1
Safety Issue:
Description:NCI CTCAE, Version 4.0
Measure:Abscopal response rate
Time Frame:2 years
Safety Issue:
Description:According to abscopal response definition

Details

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

Trial Keywords

  • Breast Cancer

Last Updated

May 1, 2018