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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03807765
• Other study ID #: MCC-19765
• Secondary ID: CA209-8NK
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 30, 2019
• Est. completion date: June 14, 2024

Study information

• Verified date: May 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: June 14, 2024
• Est. primary completion date: September 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Breast Neoplasms
• Metastatic Breast Cancer
• Neoplasm Metastasis

Intervention

Drug:
• Nivolumab
480 mg intravenous Nivolumab administered every 4 weeks.

Radiation:
• Stereotactic Radiosurgery
Patients will receive single session SRS to intact brain metastases and post-operative cavities. A linear accelerator (LINAC)-based frameless delivery system will be used to deliver the stereotactic radiation. The lesion will be defined using gadolinium enhanced MRI with 1 mm slices for treatment planning purposes prior to the delivery of radiation. The MRI image will be co-registered and fused with CT imaging. Doses will be prescribed to ensure coverage of at least 95% of the planning target volume (PTV) with the prescription dose. Treatments will be delivered using dynamic conformal arcs or intensity modulated radiotherapy.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants who experience Dose Limiting Toxicities	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.	Up to 8 weeks
Secondary	Evaluation of intracranial local brain tumor following treatment	Intracranial local brain tumor control following SRS and Nivolumab will be determined from irradiated lesions according to Response Assessment in Neuro-Oncology (RANO) criteria.	At 3, 6 and 12 months post treatment
Secondary	Evaluation of intracranial distant brain tumor following treatment	Intracranial distant brain tumor control following SRS and Nivolumab will be determined by the development of new lesions outside of the irradiated area.	At 3, 6 and 12 months post treatment
Secondary	Intracranial Progression Free Survival (PFS)	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.	Up to 12 months
Secondary	Extracranial Progression Free Survival (PFS)	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.	Up to 12 months
Secondary	Overall Survival	Overall Survival defined as time from the date of start of treatment to death.	Up to 24 months

External Links

•   Moffitt Cancer Center Clinical Trials Website