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Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients

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ClinicalTrials.gov Identifier: NCT03449238
Recruitment Status : Recruiting
First Posted : February 28, 2018
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

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 will be infused a day before SRS at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Brain Metastases Drug: Pembrolizumab Phase 1 Phase 2

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 will be infused the day before SRS, at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Intervention Model: Single Group Assignment
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 will be infused the day before SRS, at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients
Actual Study Start Date : November 15, 2018
Estimated Primary Completion Date : December 30, 2024
Estimated Study Completion Date : December 30, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
pembrolizumab and SRS
Pembrolizumab will be infused the day before SRS, at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.
Drug: Pembrolizumab
pembrolizumab will be infused the day before SRS, at the standard dose of 200mg IV over 30 minutes and repeated every 3 weeks until disease progression or unacceptable toxicity.




Primary Outcome Measures :
  1. Tumor response for non-irradiated brain lesions at 8 weeks according to RECIST1.1 [ Time Frame: 8 weeks ]
    detect abscopal responses in non-irradiated brain metastases, followed at routine post SRS brain MRI (evaluated at 8 weeks post-treatment, +/- one week) according to Response Evaluation criteria in Solid Tumors (RECIST1.1)

  2. Correlation of abscopal responses with the radiation dose received [ Time Frame: 1 year ]
    Correlate potential abscopal responses with their radiation dose exposure

  3. Overall survival - assessed from the start of study drug until death in non-irradiation metastases in the rest of the body by routine imaging. [ Time Frame: 3 years ]
    detect systemic objective responses in non-irradiated metastases in the rest of the body, by routine imaging



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Ages Eligible for Study:   19 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Patients with metastatic breast cancer
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age older than 18
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Neurological function status 0, 1, 2
  • Pre- or post-menopausal women with metastatic breast cancer, and at least 2 intracranial untreated metastases
  • A diagnostic contrast enhanced MRI demonstrating at least 2 and no more than 10 measurable lesions, (>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
  • Enrolled patients should have a two-week washout period from last systemic treatment
  • Patients who have undergone prior subtotal resection are eligible providing that residual disease is <4cm in maximum diameter
  • Continuing a concurrent use of hormonal therapy or HER2neu-targeted therapy is allowed, if the patient exhibits brain metastases progression during these treatments
  • 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
  • Current use of systemic chemotherapy
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • 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
  • Prior whole brain irradiation
  • 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 within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not 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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • 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 that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
  • 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). Note: optional based on country.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449238


Contacts
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Contact: Sharanya Chandrasekhar, M.S. 212-746-7277 shc2043@med.cornell.edu
Contact: Pragya Yadav, Ph.D 212-746-2546 pry2003@med.cornell.edu

Locations
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United States, New York
Weill Cornell Medicine Recruiting
New York, New York, United States, 10065
Contact: Sharanya Chandrasekhar, M.S.    646-962-2196    shc2043@med.cornell.edu   
Contact: Pragya Yadav, Ph.D.    646-962-2199    pry2003@med.cornell.edu   
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
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Principal Investigator: Silvia Formenti, M.D. Weill Cornell Medicine - New York Presbyterian Hospital

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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT03449238     History of Changes
Other Study ID Numbers: 1710018694
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents