Clinical Trials /

Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases

NCT03807765

Description:

This study is to find out if administration of stereotactic radiosurgery (SRS) given after Nivolumab will improve overall response rate/anti-tumor activity in patients with metastatic breast cancer with brain metastases.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases
  • Official Title: Phase Ib Study of Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases

Clinical Trial IDs

  • ORG STUDY ID: MCC-19765
  • SECONDARY ID: CA209-8NK
  • NCT ID: NCT03807765

Conditions

  • Metastatic Breast Cancer
  • Brain Metastases

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab followed by stereotactic radiosurgery (SRS)

Purpose

This study is to find out if administration of stereotactic radiosurgery (SRS) given after Nivolumab will improve overall response rate/anti-tumor activity in patients with metastatic breast cancer with brain metastases.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab followed by stereotactic radiosurgery (SRS)Experimental480 mg Nivolumab will be given intravenously every 4 weeks, followed by SRS the week after the initial dose of Nivolumab.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Provides signed and dated informed consent

          -  Stated willingness to comply with all study procedures and availability for the
             duration of the study

          -  Age 18 or older

          -  Breast cancer with brain metastases, as documented by extracranial tumor biopsy with
             MRI brain imaging or intracranial surgical pathology revealing brain metastases

          -  10 or less brain metastases eligible for SRS to brain metastases or to the
             post-operative bed

          -  Maximum diameter of the largest intact brain metastases ≤ 4 cm

          -  Eastern Cooperative Oncology Group performance status 0 to 2

          -  Prior treatment with taxane based chemotherapy with anthracyclines (if appropriate)

          -  A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of
             intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation
             should be made available and submitted to the central lab for correlative studies. If
             attempts to obtain archival tissue are unsuccessful the patient may be enrolled.

          -  Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will
             be allowed if active measurable disease has not previously been treated with radiation
             therapy

          -  Continuing concurrent use of hormonal therapy or HER2-targeted therapy is allowed if
             the patient exhibits brain metastases progression during treatment

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin)
             within 24 hours prior to the administration of each dose of study agent.

          -  WOCBP must agree to follow instructions for method(s) of contraception for the
             duration of treatment with study drug(s), plus 5 half-lives of study drug (half-life
             up to 25 days), plus 30 days (duration of ovulatory cycle) for a total of 5 months
             after treatment completion.

        Exclusion Criteria:

          -  Presence of leptomeningeal disease

          -  Prior whole brain radiation therapy

          -  All toxicities attributed to prior anticancer therapy must have been resolved to Grade
             1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) . Some
             exceptions apply.

          -  Women who are pregnant or breastfeeding

          -  Active, known, or suspected autoimmune disease. Patients with an autoimmune
             paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded.
             Some exceptions apply.

          -  Prior therapy with antiPD-1, antiPD-L1, antiPD-L2, antiCD137, or antiCTLA-4 antibody
             (including ipilimumab or any other antibody or drug specifically targeting T-cell
             co-stimulation or checkpoint pathways)

          -  Interstitial lung disease that is symptomatic or may interfere with the detection or
             management of suspected drug-related pulmonary toxicity

          -  Any patient requiring supplemental oxygen therapy

          -  Patients with prior history of non-breast cancer malignancies are excluded except in
             the case of adequately treated basal cell cancer, squamous cell skin cancer, chronic
             lymphocytic leukemia, or other indolent diseases not requiring therapy

          -  Known medical condition that, in the investigator's opinion, would increase the risk
             associated with study participation or study drug(s) administration or that would
             interfere with the interpretation of safety results

          -  Major surgery or significant traumatic injury that has not been recovered from by 14
             days before the initiation of study drug

          -  Current or prior participation in a study of an investigational agent or
             investigational device within 2 weeks of first dose of study treatment

          -  Positive test for: a. Hepatitis B virus using Hepatitis B virus surface antigen
             (Hepatitis B virus surface antigen) test b. Hepatitis C virus (HCV) using HCV
             ribonucleic acid or HCV antibody test that indicates acute or chronic infection c.
             Exception: Individuals with a positive test for HCV antibody but no detection of HCV
             ribonucleic acid indicating no current infection are eligible

          -  Medical history of testing positive for HIV or AIDS. No HIV testing is required,
             unless mandated by a local health authority.

          -  Inadequate hematologic function

          -  Inadequate hepatic function

          -  Inadequate pancreatic function

          -  History of allergy or hypersensitivity to any of the study drugs or study drug
             components

          -  Individuals who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants who experience Dose Limiting Toxicities
Time Frame:Up to 8 weeks
Safety Issue:
Description:Neurologic dose limiting toxicities will be defined as: Symptomatic radionecrosis, >/= Grade 3 headache, >/= Grade 3 memory impairment, New onset >/= grade 3 seizures. 3 participants will be enrolled with an 8 week safety observation period. If no patients develop unacceptable neurologic toxicity attributable to SRS, the study will proceed. If 1 patient develops unacceptable neurologic toxicity among the first 3, an additional 3 patients will be enrolled to determine the rate of unacceptable toxicity with 6 patients. If no more patients develop unacceptable neurologic toxicities among the first 6 patients, the study will proceed with a dose expansion of 6 patients. If 2 or more patients develop unacceptable neurologic toxicity among the first 3 or 6 patients, the dose of radiation therapy will be adjusted. If excessive toxicities are noted with radiation dose level -1, treatment will proceed with nivolumab alone.

Secondary Outcome Measures

Measure:Evaluation of intracranial local brain tumor following treatment
Time Frame:At 3, 6 and 12 months post treatment
Safety Issue:
Description:Intracranial local brain tumor control following SRS and Nivolumab will be determined from irradiated lesions according to Response Assessment in Neuro-Oncology (RANO) criteria.
Measure:Evaluation of intracranial distant brain tumor following treatment
Time Frame:At 3, 6 and 12 months post treatment
Safety Issue:
Description:Intracranial distant brain tumor control following SRS and Nivolumab will be determined by the development of new lesions outside of the irradiated area.
Measure:Intracranial Progression Free Survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
Description:Time from the date of start of treatment to the investigator-determined date of progression (determined by RANO) or death due to any cause, whichever occurs first.
Measure:Extracranial Progression Free Survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
Description:Time from the date of start of treatment to the investigator determined date of progression (determined by Immune-Related Response Evaluation Criteria in Solid Tumors [irRECIST]) or death due to any cause, whichever occurs first.
Measure:Overall Survival
Time Frame:Up to 24 months
Safety Issue:
Description:Overall Survival defined as time from the date of start of treatment to death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • breast cancer
  • brain metastases

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