Atezolizumab + Stereotactic Radiation in Triple-negative Breast Cancer and Brain Metastasis

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ClinicalTrials.gov Identifier: NCT03483012

Recruitment Status : Active, not recruiting

First Posted : March 29, 2018

Results First Posted : December 22, 2023

Last Update Posted : December 22, 2023

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Sponsor:

Collaborator:

Genentech, Inc.

Information provided by (Responsible Party):

Nancy Lin, MD, Dana-Farber Cancer Institute

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Breast Cancer
Interventions	Drug: Atezolizumab Procedure: Stereotactic radiosurgery (SRS)
Enrollment	6

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Atezolizumab + Stereotactic Radiosurgery (SRS)
Arm/Group Description	Atezolizumab administered intraveno...
Arm/Group Description	Atezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained Atezolizumab: Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway Stereotactic radiosurgery (SRS): Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors
Period Title: Overall Study
Started	6
Completed	0
Not Completed	6
Reason Not Completed
Lack of Efficacy	6

Baseline Characteristics

Arm/Group Title		Atezolizumab + Stereotactic Radiosurgery (SRS)
Arm/Group Description		Atezolizumab administered intraveno...
Arm/Group Description		Atezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained Atezolizumab: Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway Stereotactic radiosurgery (SRS): Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors
Overall Number of Baseline Participants		6
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	6 participants
		46 (32 to 69)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
Age category	Number Analyzed	6 participants
	<50	4 66.7%
	>=50	2 33.3%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	Female	6 100.0%
	Male	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	5 83.3%
	More than one race	0 0.0%
	Unknown or Not Reported	1 16.7%
Eastern Cooperative Oncology Group (ECOG) performance status Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	0-Fully active, able to carry on pre-disease performance without restriction	5 83.3%
	1-Restricted in strenuous physical activity but able to perform work of a light or sedentary nature	1 16.7%
Stage at initial diagnosis Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	I- Cancer has spread to other tissue in small area	1 16.7%
	II- Tumor is 20-50mm with some lymph node involvement, or tumor is >50mm with no nodal involvement	4 66.7%
	Not IV but otherwise unknown- Non-metastatic but stage otherwise unknown	1 16.7%
Disease-free interval (interval from primary diagnosis date to metastatic diagnosis date) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	<2 years	2 33.3%
	>=2 years	4 66.7%
Hormone receptor status of primary tumor Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	ER positive/PR negative	1 16.7%
	ER and PR negative	5 83.3%
Hormone receptor status of metastatic tumor Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	ER and PR negative	1 16.7%
	Not done	5 83.3%
HER-2 status of primary tumor (IHC) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	Negative (0,1+)	4 66.7%
	Equivocal (2+)	1 16.7%
	Not done	1 16.7%
HER-2 status of primary tumor (ISH) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	Negative (copy number <4 and HER2/CEP17 ratio <2.0)	4 66.7%
	Not done	2 33.3%
Measurable disease by RECIST 1.1 at baseline Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	Yes	5 83.3%
	No	1 16.7%
Prior adjuvant or neoadjuvant endocrine therapy Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	Yes	3 50.0%
	No	3 50.0%
Prior lines of chemotherapy for metastasis or recurrence Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	6 participants
	0 lines	2 33.3%
	1 line	3 50.0%
	>=2 lines	1 16.7%

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival
Description	Defined as time from first dose of atezolizumab (day 1 cycle 1) to pro...
Description	Defined as time from first dose of atezolizumab (day 1 cycle 1) to progression or death due to any cause. Progression is defined according to the bi-compartmental model proposed in the RANO-BM publication, and is defined as the first detection of radiologic progression of intracranial (per RANO-BM criteria), extracranial (per RECIST 1.1 criteria), or both or unequivocal progression of non-measurable disease in the opinion of the treating physician; with each compartment (CNS and non-CNS) assessed separately
Time Frame	Assessed from the first dose of atezolizumab until the date of first documented progression according to RANO-BM or date of death from any cause, whichever came first, for a maximum of 1.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Atezolizumab + Stereotactic Radiosurgery (SRS)
Arm/Group Description:	Atezolizumab administered intraveno...
Arm/Group Description:	Atezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained Atezolizumab: Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway Stereotactic radiosurgery (SRS): Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors
Overall Number of Participants Analyzed	6
Median (95% Confidence Interval) Unit of Measure: weeks
	5.8 ^[1] (4.1 to NA)

[1]

Insufficient sample size/number of events

2.Secondary Outcome


Title	Extracranial Objective Response Rate
Description	Defined as the percentage of patients achieving a complete response (c...
Description	Defined as the percentage of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1
Time Frame	Assessed from the first dose of atezolizumab until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, for a maximum of 1.5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Atezolizumab + Stereotactic Radiosurgery (SRS)
Arm/Group Description:	Atezolizumab administered intraveno...
Arm/Group Description:	Atezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained Atezolizumab: Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway Stereotactic radiosurgery (SRS): Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors
Overall Number of Participants Analyzed	6
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of patients
	0 (0 to 45.9)

3.Secondary Outcome


Title	Overall Survival
Description	Defined as the time from first dose of atezolizumab (day 1 cycle 1) to...
Description	Defined as the time from first dose of atezolizumab (day 1 cycle 1) to death from any cause. Patients who are alive at the end of the study are censored at the date of last known alive.
Time Frame	Assessed from the first dose of atezolizumab to the date of death from any cause or date last known alive, for a maximum of 3.8 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Atezolizumab + Stereotactic Radiosurgery (SRS)
Arm/Group Description:	Atezolizumab administered intraveno...
Arm/Group Description:	Atezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained Atezolizumab: Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway Stereotactic radiosurgery (SRS): Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors
Overall Number of Participants Analyzed	6
Median (95% Confidence Interval) Unit of Measure: weeks
	42.4 ^[1] (15.7 to NA)

[1]

Insufficient sample size/number of events

Adverse Events

Time Frame	Adverse event data were collected on the first day of each treatment cycle, at the end of treatment, and up to 30 days post-end of treatment, for up to a maximum of 1.8 years. Death events were assessed for up to a maximum of 3.8 years.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Atezolizumab + Stereotactic Radiosurgery (SRS)
Arm/Group Description	Atezolizumab administered intraveno...
Arm/Group Description	Atezolizumab administered intravenously once every 3 weeks Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained Atezolizumab: Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway Stereotactic radiosurgery (SRS): Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors
All-Cause Mortality
	Atezolizumab + Stereotactic Radiosurgery (SRS)
	Affected / at Risk (%)
Total	5/6 (83.33%)
Serious Adverse Events Serious Adverse Events
	Atezolizumab + Stereotactic Radiosurgery (SRS)
	Affected / at Risk (%)
Total	2/6 (33.33%)
Nervous system disorders
Intracranial hemorrhage ^† 1	1/6 (16.67%)
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	1/6 (16.67%)
Pleural effusion ^† 1	1/6 (16.67%)
1 Term from vocabulary, CTCAE (4.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Atezolizumab + Stereotactic Radiosurgery (SRS)
	Affected / at Risk (%)
Total	5/6 (83.33%)
Endocrine disorders
Cushingoid ^† 1	1/6 (16.67%)
Gastrointestinal disorders
Abdominal pain ^† 1	1/6 (16.67%)
Bloating ^† 1	1/6 (16.67%)
Constipation ^† 1	1/6 (16.67%)
Dyspepsia ^† 1	1/6 (16.67%)
Nausea ^† 1	2/6 (33.33%)
Vomiting ^† 1	1/6 (16.67%)
General disorders
Fatigue ^† 1	3/6 (50.00%)
Fever ^† 1	2/6 (33.33%)
Flu like symptoms ^† 1	1/6 (16.67%)
Non-cardiac chest pain ^† 1	1/6 (16.67%)
Pain ^† 1	1/6 (16.67%)
Infections and infestations
Pharyngitis ^† 1	1/6 (16.67%)
Urinary tract infection ^† 1	1/6 (16.67%)
Vaginal infection ^† 1	1/6 (16.67%)
Investigations
Alanine aminotransferase increased ^† 1	1/6 (16.67%)
Alkaline phosphatase increased ^† 1	1/6 (16.67%)
Aspartate aminotransferase increased ^† 1	2/6 (33.33%)
Weight loss ^† 1	1/6 (16.67%)
Metabolism and nutrition disorders
Anorexia ^† 1	2/6 (33.33%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness ^† 1	2/6 (33.33%)
Muscle weakness left-sided ^† 1	1/6 (16.67%)
Myalgia ^† 1	1/6 (16.67%)
Nervous system disorders
Ataxia ^† 1	1/6 (16.67%)
Cognitive disturbance ^† 1	1/6 (16.67%)
Headache ^† 1	1/6 (16.67%)
Paresthesia ^† 1	1/6 (16.67%)
Seizure ^† 1	1/6 (16.67%)
Reproductive system and breast disorders
Vaginal discharge ^† 1	1/6 (16.67%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	3/6 (50.00%)
Dyspnea ^† 1	1/6 (16.67%)
Respiratory, thoracic and mediastinal disorders ^† 1	1/6 (16.67%)
Skin and subcutaneous tissue disorders
Rash maculo-papular ^† 1	1/6 (16.67%)
1 Term from vocabulary, CTCAE (4.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Sara Tolaney, MD, MPH
Organization:	Dana-Farber Cancer Institute
Phone:	617-632-5743
EMail:	Sara_Tolaney@dfci.harvard.edu

Layout table for additonal information

Responsible Party:	Nancy Lin, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT03483012
Other Study ID Numbers:	17-519
First Submitted:	February 28, 2018
First Posted:	March 29, 2018
Results First Submitted:	July 7, 2023
Results First Posted:	December 22, 2023
Last Update Posted:	December 22, 2023

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