Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases
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|ClinicalTrials.gov Identifier: NCT03807765|
Recruitment Status : Recruiting
First Posted : January 17, 2019
Last Update Posted : November 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer Brain Metastases||Drug: Nivolumab Radiation: Stereotactic Radiosurgery||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib Study of Stereotactic Radiation and Nivolumab in the Management of Metastatic Breast Cancer Brain Metastases|
|Actual Study Start Date :||January 14, 2019|
|Estimated Primary Completion Date :||January 14, 2021|
|Estimated Study Completion Date :||January 14, 2022|
Experimental: Nivolumab followed by stereotactic radiosurgery (SRS)
480 mg Nivolumab will be given intravenously every 4 weeks, followed by SRS the week after the initial dose of Nivolumab.
480 mg intravenous Nivolumab administered every 4 weeks.
Other Name: Opdivo
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.
- Number of Participants who experience Dose Limiting Toxicities [ Time Frame: Up to 8 weeks ]
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.
- Evaluation of intracranial local brain tumor following treatment [ Time Frame: At 3, 6 and 12 months post 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.
- Evaluation of intracranial distant brain tumor following treatment [ Time Frame: At 3, 6 and 12 months post treatment ]Intracranial distant brain tumor control following SRS and Nivolumab will be determined by the development of new lesions outside of the irradiated area.
- Intracranial Progression Free Survival (PFS) [ Time Frame: Up to 12 months ]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.
- Extracranial Progression Free Survival (PFS) [ Time Frame: Up to 12 months ]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.
- Overall Survival [ Time Frame: Up to 24 months ]Overall Survival defined as time from the date of start of treatment to death.
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): NCT03807765
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Michelle DeJesus 813-745-6911 Michelle.DeJesus@Moffitt.org|
|Principal Investigator: Kamran Ahmed, MD|
|Principal Investigator: Heather Han, MD|
|Sub-Investigator: John Arrington, MD|
|Sub-Investigator: Jimmy Caudell, MD, PhD|
|Sub-Investigator: Ricardo Costa, MD, MSc|
|Sub-Investigator: Brian Czerniecki, MD, PhD|
|Sub-Investigator: Roberto Diaz, MD, PhD|
|Sub-Investigator: Arnold Etame, MD, PhD|
|Sub-Investigator: Peter Forsyth, MD|
|Sub-Investigator: Roohi Ismail-Khan, MD, MSc|
|Sub-Investigator: Hung Khong, MD|
|Sub-Investigator: Sungjune Kim, MD, PhD|
|Sub-Investigator: Loretta Loftus, MD, MBA|
|Sub-Investigator: Timothy Robinson, MD, PhD|
|Sub-Investigator: Marilin Rosa, MD|
|Sub-Investigator: Solmaz Sahebjam, MD|
|Sub-Investigator: Hatem Soliman, MD|
|Sub-Investigator: Michael Yu, MD|
|Sub-Investigator: Nam Tran, MD, PhD|
|Principal Investigator:||Kamran Ahmed, MD||H. Lee Moffitt Cancer Center and Research Institute|