Clinical trial NCT03449238: Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients
Official title: Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Brain Metastases
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-02-28
Enrollment: 41
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with metastatic breast cancer with at least 2 brain metastases, eligible to receive SRS. Patients will complete radiation therapy within 1 week and Pembrolizumab may be continued every 3 weeks until evidence of brain progression or serious adverse toxicity. Patients will be followed until death.

Pembrolizumab infusion will be given on Day 4 (+/-1) after SRS treatment at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.
Primary purpose: TREATMENT

Brief summary: Patients with metastatic breast cancer with at least 2 brain metastases will receive pembrolizumab every 3 weeks. Patients will undergo stereotactic radiosurgery (SRS) to one of the brain lesions. Pembrolizumab infusion will be given on Day 4 (+/-1) after SRS treatment at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Detailed description: Patients with metastatic breast cancer with at least 2 brain metastases, eligible to receive SRS. Patients will complete radiation therapy within 1 week and Pembrolizumab may be continued every 3 weeks until evidence of brain progression or serious adverse toxicity. Patients will be followed until death.

Pembrolizumab infusion will be given on Day 4 (+/-1) after SRS treatment at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Eligibility criteria: Inclusion Criteria:

* Age older than 18
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Neurological function status 0, 1, 2
* Men and/or pre- or post-menopausal women with metastatic breast cancer with at least 2 intracranial untreated and measurable (≥ 5mm) metastases as visualized on brain MRI
* A diagnostic contrast enhanced MRI demonstrating at least 2 and no more than 10 measurable lesions in the brain, (≥5mm in size), performed within two weeks prior to treatment
* Maximum diameter of treated lesions should be \<4cm in size
* Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document
* Prior SRS is permitted, however the lesions targeted for treatment on trial need to be previously untreated by SRS
* Patients who have undergone prior subtotal resection are eligible providing that residual disease is \<4cm in maximum diameter: the cavity will be treated as - - - Continuing a concurrent use of hormonal therapy or anti-Her2 neu therapy is allowed, if the patient exhibits brain metastases progression during these treatments
* Enrolled patients should have a two-week washout period from last systemic treatment
* The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
* Contraception duration of 120 days
* Adequate bone marrow reserve and liver function

Exclusion Criteria:

* Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy
* Patients who have undergone complete resection of all known brain metastases
* Inability to obtain histologic proof of breast cancer
* Target lesion metastasis within 5mm of the optic apparatus so that some portion of the optic nerve or chiasm would be included in the SRS field
* Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy (second primary) that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 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 a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy..Has a known history of Human Immunodeficiency Virus (HIV).
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
* Has a known history of active TB (Bacillus Tuberculosis).
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

Primary outcomes:
measure: Tumor response for non-irradiated brain lesions at 8 weeks according to RECIST1.1
timeFrame: 8 weeks
measure: Correlation of abscopal responses with the radiation dose received
timeFrame: 1 year
measure: Overall survival - assessed from the start of study drug until death in non-irradiation metastases in the rest of the body by routine imaging.
timeFrame: 3 years
Secondary outcomes:
measure: Number of participants with abscopal response will be assessed.
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Brooklyn Methodist Hospital - NewYork Presbyterian
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Queens
state: New York
Study officials:
affiliation: Weill Cornell Medicine - New York Presbyterian Hospital
name: Silvia Formenti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: