Atezolizumab + Pertuzumab + Trastuzumab In CNS Mets In BC

• ClinicalTrials.gov Identifier: NCT03417544
• Recruitment Status: Active, not recruiting
• First Posted: January 31, 2018
• Results First Posted: May 7, 2024
• Last Update Posted: May 7, 2024
• Sponsor: Nancy Lin, MD
• 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
• Conditions: HER2-positive Metastatic Breast Cancer; Central Nervous System Metastases
• Interventions: Drug: ATEZOLIZUMAB; Drug: PERTUZUMAB; Drug: TRASTUZUMAB
• Enrollment: 19

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description	Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Period Title: Overall Study
Started	19
Completed	19
Not Completed	0

Baseline Characteristics

Arm/Group Title		ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description		Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Baseline Participants		19
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	19 participants
		50; (35 to 71)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Female	19 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	19 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 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	2 10.5%
	White	17 89.5%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
ECOG PS [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	0	12 63.2%
	1	7 36.8%
		[1] Measure Description: ECOG PS stands for Eastern Cooperative Oncology Group Performance Status, which is a scale used to assess how a patient's disease is progressing and how it affects their daily living abilities. The score is discrete and in the range of 0 to 5, higher score indicates worse patient performance.
Stage at Initial Diagnosis [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	I	1 5.3%
	II	5 26.3%
	III	5 26.3%
	IV	5 26.3%
	Not IV, but otherwise unknown	3 15.8%
		[1] Measure Description: The clinical stage at initial diagnosis in breast cancer is typically described using the TNM staging system, which takes into account the size of the primary tumor (T), whether the cancer has spread to nearby lymph nodes (N), and whether it has metastasized (spread to distant organs or tissues) (M). The stage is described as Roman numerals from 0 to IV, with higher numbers indicating a more advanced stage of cancer.
Hormone Receptor Status of Primary Tumor [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	ER and PR positive	7 36.8%
	ER positive/PR negative	2 10.5%
	ER negative/PR positive	1 5.3%
	ER and PR negative	9 47.4%
		[1] Measure Description: The Hormone Receptor Status of a primary breast tumor is defined using estrogen receptor (ER) and progesterone receptor (PR) status. HR-positive tumors were defined as having either ER-positive and/or PR-positive cells, while HR-negative tumors were defined as having neither ER-positive nor PR-positive cells.
Hormone Receptor Status of Metastatic Tumor [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	ER and PR positive	1 5.3%
	ER positive/PR negative	2 10.5%
	ER negative/PR positive	1 5.3%
	ER and PR negative	10 52.6%
	Unknown	5 26.3%
		[1] Measure Description: The Hormone Receptor Status of Metastatic Tumor is defined using estrogen receptor (ER) and progesterone receptor (PR) status. HR-positive tumors were defined as having either ER-positive and/or PR-positive cells, while HR-negative tumors were defined as having neither ER-positive nor PR-positive cells.
HER-2 Status of Primary Tumor (IHC) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Negative (0,1+)	2 10.5%
	Equivocal (2+)	0 0.0%
	Positive (3+)	13 68.4%
	Not Done	4 21.1%
		[1] Measure Description: HER-2, also known as human epidermal growth factor receptor 2, is a protein that promotes the growth of cancer cells. The primary tumor was HER-2 positive by immunohistochemistry (IHC), indicating overexpression of the HER-2 protein. The primary tumor was HER-2 negative by immunohistochemistry (IHC), indicating no or low expression of the HER-2 protein.
HER-2 Status of Primary Tumor (FISH) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Equivocal (4<= copy number <6 and HER2/CEP17 ratio <2.0)	1 5.3%
	Positive (copy number >=6 or HER2/CEP17 ratio >=2.0)	8 42.1%
	Not Done	10 52.6%
		[1] Measure Description: HER-2 status of a primary breast tumor can also be determined using fluorescence in situ hybridization (FISH), which is another laboratory test that provides information about the HER-2 gene. The primary tumor was HER-2 positive by FISH, indicating amplification of the HER-2 gene. The primary tumor was HER-2 negative by FISH, indicating no amplification of the HER-2 gene.
Measurable Disease by RECIST 1.1; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Yes	7 36.8%
	No	12 63.2%
Tissue Available at Baseline; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Yes	17 89.5%
	No	2 10.5%
Sites of Disease at Study Entry; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Breast or chest wall	18 94.7%
	Other	1 5.3%
Lines of Chemotherapy for Metastasis or Recurrence; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	None	1 5.3%
	1 line	4 21.1%
	2 lines	6 31.6%
	> 2 lines	8 42.1%
Use of Corticosteroids; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Yes	5 26.3%
	No	14 73.7%
Prior Brain Surgery; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants
	Yes	6 31.6%
	No	13 68.4%

Outcome Measures

1. Primary Outcome

Title	Confirmed Overall Response Rate in CNS
Description	The proportion of patients who had confirmed complete response or confirmed partial response, assessed using neuro-oncology-brain metastases (RANO-BM) criteria. RANO-BM assess the response of brain metastases to treatment, using MRI scan. There are four categories as results: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD), which is separately defined as disappearance of all target lesions, at least a 30% decrease in the sum of the diameters of target lesions, neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease (PD) and at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest) or the appearance of one or more new lesions.
Time Frame	Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:	Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
	2 10.5%

2. Secondary Outcome

Title	Objective Non-CNS Response Rates
Description	The proportion of patients who had confirmed complete response or partial response, according to response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. RECIST is used to assess the response of solid tumors to treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
Time Frame	Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:	Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
	1 5.3%

3. Secondary Outcome

Title	Clinical Benefit Rate in CNS at 18 Weeks
Description	The proportion of patients who had stable disease, confirmed partial response or complete response, respectively, >=18 weeks, according to RANO-BM criteria
Time Frame	Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:	Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
	8 42.1%

4. Secondary Outcome

Title	Patient Reported Outcomes by MDASI-BT Stratified by CBR at 18 Weeks
Description	Evaluated by M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT). MDASI-BT assess 13 symptom items and 6 interference items from the core MDAST as well as 9 symptoms specific to brain tumors, and generate Symptom Severity Score (SSS) and Symptom Interference Score (SIS) separately. The scale of the scores are in a range of 0 to 10, where 0 represents "not present" or "not severe," and 10 represents "as bad as you can imagine" or "most severe." A higher score indicates a higher level of symptom severity. Mean of the scores are reported across groups with and without CBR at 18 weeks and in baseline, week 9 and week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

We only report the SSS and SIS scores that are available and stratified by with or without CBR at 18 weeks, thus the sample size in different categories differ from the overall sample size

Arm/Group Title		ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:		Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: score on a scale
SSS Score for patients with CBR at 18 weeks at Baseline	Number Analyzed	7 participants
		1.8 (1.2)
SSS Score for patients with CBR at 18 weeks at Week 9	Number Analyzed	7 participants
		1.5 (0.9)
SSS Score for patients with CBR at 18 weeks at Week 24	Number Analyzed	6 participants
		1.7 (1.3)
SSS Score for patients without CBR at 18 weeks at Baseline	Number Analyzed	11 participants
		1.9 (1.2)
SSS Score for patients without CBR at 18 weeks at Week 9	Number Analyzed	8 participants
		1.9 (1.1)
SSS Score for patients without CBR at 18 weeks at Week 24	Number Analyzed	10 participants
		2.5 (1.4)
SIS Score for patients with CBR at 18 weeks at Baseline	Number Analyzed	7 participants
		4.0 (2.3)
SIS Score for patients with CBR at 18 weeks at Week 9	Number Analyzed	7 participants
		2.8 (2.6)
SIS Score for patients with CBR at 18 weeks at Week 24	Number Analyzed	6 participants
		2.6 (3.4)
SIS Score for patients without CBR at 18 weeks at Baseline	Number Analyzed	11 participants
		2.2 (2.1)
SIS Score for patients without CBR at 18 weeks at Week 9	Number Analyzed	8 participants
		2.4 (2.4)
SIS Score for patients without CBR at 18 weeks at Week 24	Number Analyzed	10 participants
		4.2 (2.9)

5. Secondary Outcome

Title	Patient Reported Outcomes by EQ-5D Stratified by CBR at 18 Weeks
Description	Evaluated by EuroQol Five Dimension Questionnaire (EQ-5D) evaluations assessments to assess the general health status of patients enrolled in the study. EQ-5D scores are assessed with five dimensions with the range of 0 to 5, and a higher score indicates worse health. Mean of the scores are reported across groups with and without CBR at 18 weeks and in baseline, week 9 and week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

We only report the EQ-5D scores that are available and stratified by with or without CBR at 18 weeks, thus the sample size in different categories differ from the overall sample size

Arm/Group Title		ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:		Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: units on a scale
Patients with CBR at 18 weeks at Baseline	Number Analyzed	7 participants
		0.7 (0.5)
Patients with CBR at 18 weeks at Week 9	Number Analyzed	8 participants
		0.5 (0.4)
Patients with CBR at 18 weeks at Week 24	Number Analyzed	6 participants
		0.7 (0.9)
Patients without CBR at 18 weeks at Baseline	Number Analyzed	11 participants
		0.9 (0.7)
Patients without CBR at 18 weeks at Week 9	Number Analyzed	8 participants
		0.8 (0.4)
Patients without CBR at 18 weeks at Week 24	Number Analyzed	10 participants
		1.4 (0.7)

6. Secondary Outcome

Title	Investigator-Assessed Neurological Evaluation (NANO) Stratified by CBR at 18 Weeks
Description	Evaluated by physician assessed Neurological Assessment in Neuro-Oncology (NANO) scale. The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during visits. The score defines overall response criteria and is with the range of 0 to 4. Higher score means worse response to the treatment. Mean of the scores are reported across groups with and without CBR at 18 weeks and in baseline, week 9 and week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

We only report the NANO scores that are available and stratified by with or without CBR at 18 weeks, thus the sample size in different categories differ from the overall sample size

Arm/Group Title		ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:		Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: units on a scale
Patients with CBR at 18 weeks at Baseline	Number Analyzed	8 participants
		0.03 (0.08)
Patients with CBR at 18 weeks at Week 9	Number Analyzed	8 participants
		0.1 (0.13)
Patients with CBR at 18 weeks at Week 24	Number Analyzed	5 participants
		0.17 (0.27)
Patients without CBR at 18 weeks at Baseline	Number Analyzed	10 participants
		0.1 (0.14)
Patients without CBR at 18 weeks at Week 9	Number Analyzed	10 participants
		0.18 (0.24)
Patients without CBR at 18 weeks at Week 24	Number Analyzed	9 participants
		0.39 (0.27)

7. Secondary Outcome

Title	Clinical Benefit Rate in CNS at 24 Weeks
Description	The proportion of patients who had stable disease, confirmed partial response or complete response, respectively, >=24 weeks, according to RANO-BM criteria
Time Frame	Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description:	Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Overall Number of Participants Analyzed	19
Measure Type: Count of Participants; Unit of Measure: Participants
	6 31.6%

Adverse Events

Time Frame	All adverse events were reported after initiation of study treatment and until 30 days after the last dose of study treatment or until initiation of new systemic anti-cancer therapy, an average of one and a half years
Adverse Event Reporting Description	Serious Adverse Events are defined as any events with grade 3 or higher. Other Adverse Events include any grade 1 and 2 events and those exceed 5% frequency threshold are reported.
Arm/Group Title	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
Arm/Group Description	Patients will receive the following treatment: Atezolizumab (IV) every 3 weeks (q3w)]; Pertuzumab (loading dose ), followed q3w thereafter by a predetermined dose in the protocol via IV); High-dose Trastuzumab weekly for the first 24 weeks, and thereafter trastuzumab q3w). ATEZOLIZUMAB: (IV) every 3 weeks PERTUZUMAB: Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV TRASTUZUMAB: Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
All-Cause Mortality
	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
	Affected / at Risk (%)
Total	1/19 (5.26%)
Serious Adverse Events
	ATEZOLIZUMAB, PERTUZUMAB, TRASTUZUMAB
	Affected / at Risk (%)
Total	10/19 (52.63%)
Blood and lymphatic system disorders
Anemia † 1	3/19 (15.79%)
Cardiac disorders
Heart failure † 1	1/19 (5.26%)
Gastrointestinal disorders
Abdominal pain † 1	1/19 (5.26%)
Diarrhea † 1	2/19 (10.53%)
General disorders
Death NOS † 1	1/19 (5.26%)
Fatigue † 1	1/19 (5.26%)
Hepatobiliary disorders
Portal vein thrombosis † 1	1/19 (5.26%)
Infections and infestations
Urinary tract infection † 1	1/19 (5.26%)
Investigations
Lymphocyte count decreased † 1	2/19 (10.53%)
Platelet count decreased † 1	1/19 (5.26%)
Weight loss † 1	1/19 (5.26%)
Metabolism and nutrition disorders
Hyperglycemia † 1	2/19 (10.53%)
Hypokalemia † 1	1/19 (5.26%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness † 1	1/19 (5.26%)
Nervous system disorders
Edema cerebral † 1	2/19 (10.53%)
Headache † 1	1/19 (5.26%)
Seizure † 1	1/19 (5.26%)
Psychiatric disorders
Confusion † 1	1/19 (5.26%)
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	1/19 (5.26%)
Vascular disorders
Hypertension † 1	2/19 (10.53%)
Thromboembolic event † 1	1/19 (5.26%)
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, PERTUZUMAB, TRASTUZUMAB
	Affected / at Risk (%)
Total	19/19 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	5/19 (26.32%)
Lymph node pain † 1	1/19 (5.26%)
Cardiac disorders
Cardiac disorders - Other, specify † 1	1/19 (5.26%)
Sinus bradycardia † 1	2/19 (10.53%)
Sinus tachycardia † 1	2/19 (10.53%)
Ear and labyrinth disorders
Ear pain † 1	1/19 (5.26%)
Tinnitus † 1	1/19 (5.26%)
Endocrine disorders
Endocrine disorders - Other, specify † 1	1/19 (5.26%)
Hyperthyroidism † 1	1/19 (5.26%)
Hypothyroidism † 1	5/19 (26.32%)
Eye disorders
Blurred vision † 1	2/19 (10.53%)
Dry eye † 1	1/19 (5.26%)
Eye disorders - Other, specify † 1	2/19 (10.53%)
Optic nerve disorder † 1	1/19 (5.26%)
Gastrointestinal disorders
Abdominal pain † 1	2/19 (10.53%)
Bloating † 1	1/19 (5.26%)
Colitis † 1	1/19 (5.26%)
Constipation † 1	7/19 (36.84%)
Diarrhea † 1	11/19 (57.89%)
Dry mouth † 1	1/19 (5.26%)
Dyspepsia † 1	3/19 (15.79%)
Dysphagia † 1	2/19 (10.53%)
Fecal incontinence † 1	1/19 (5.26%)
Flatulence † 1	1/19 (5.26%)
Gastric ulcer † 1	1/19 (5.26%)
Nausea † 1	10/19 (52.63%)
Vomiting † 1	6/19 (31.58%)
General disorders
Chills † 1	1/19 (5.26%)
Edema limbs † 1	1/19 (5.26%)
Fatigue † 1	16/19 (84.21%)
Fever † 1	2/19 (10.53%)
Gait disturbance † 1	5/19 (26.32%)
Malaise † 1	1/19 (5.26%)
Pain † 1	6/19 (31.58%)
Immune system disorders
Immune system disorders - Other, specify † 1	1/19 (5.26%)
Infections and infestations
Infections and infestations - Other, specify † 1	2/19 (10.53%)
Lung infection † 1	1/19 (5.26%)
Papulopustular rash † 1	1/19 (5.26%)
Paronychia † 1	1/19 (5.26%)
Urinary tract infection † 1	1/19 (5.26%)
Vaginal infection † 1	1/19 (5.26%)
Injury, poisoning and procedural complications
Bruising † 1	1/19 (5.26%)
Fall † 1	5/19 (26.32%)
Injury, poisoning and procedural complications - Other, specify † 1	1/19 (5.26%)
Investigations
Activated partial thromboplastin time prolonged † 1	1/19 (5.26%)
Alanine aminotransferase increased † 1	3/19 (15.79%)
Alkaline phosphatase increased † 1	4/19 (21.05%)
Aspartate aminotransferase increased † 1	9/19 (47.37%)
Blood bilirubin increased † 1	1/19 (5.26%)
Creatinine increased † 1	1/19 (5.26%)
Ejection fraction decreased † 1	2/19 (10.53%)
Lymphocyte count decreased † 1	7/19 (36.84%)
Neutrophil count decreased † 1	3/19 (15.79%)
Platelet count decreased † 1	3/19 (15.79%)
Weight gain † 1	4/19 (21.05%)
Weight loss † 1	3/19 (15.79%)
White blood cell decreased † 1	4/19 (21.05%)
Metabolism and nutrition disorders
Anorexia † 1	4/19 (21.05%)
Dehydration † 1	1/19 (5.26%)
Hyperglycemia † 1	8/19 (42.11%)
Hypoalbuminemia † 1	6/19 (31.58%)
Hypocalcemia † 1	4/19 (21.05%)
Hypokalemia † 1	3/19 (15.79%)
Hyponatremia † 1	1/19 (5.26%)
Metabolism and nutrition disorders - Other, specify † 1	3/19 (15.79%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	5/19 (26.32%)
Arthritis † 1	1/19 (5.26%)
Back pain † 1	4/19 (21.05%)
Bone pain † 1	2/19 (10.53%)
Generalized muscle weakness † 1	4/19 (21.05%)
Joint range of motion decreased † 1	1/19 (5.26%)
Muscle weakness left-sided † 1	1/19 (5.26%)
Muscle weakness lower limb † 1	1/19 (5.26%)
Muscle weakness upper limb † 1	1/19 (5.26%)
Musculoskeletal and connective tissue disorder - Other, specify † 1	1/19 (5.26%)
Myalgia † 1	1/19 (5.26%)
Neck pain † 1	2/19 (10.53%)
Nervous system disorders
Ataxia † 1	5/19 (26.32%)
Cognitive disturbance † 1	3/19 (15.79%)
Concentration impairment † 1	2/19 (10.53%)
Dizziness † 1	4/19 (21.05%)
Dysarthria † 1	1/19 (5.26%)
Dysesthesia † 1	2/19 (10.53%)
Facial muscle weakness † 1	2/19 (10.53%)
Headache † 1	11/19 (57.89%)
Memory impairment † 1	4/19 (21.05%)
Nervous system disorders - Other, specify † 1	2/19 (10.53%)
Paresthesia † 1	2/19 (10.53%)
Peripheral motor neuropathy † 1	3/19 (15.79%)
Peripheral sensory neuropathy † 1	4/19 (21.05%)
Seizure † 1	2/19 (10.53%)
Somnolence † 1	1/19 (5.26%)
Spasticity † 1	1/19 (5.26%)
Tremor † 1	3/19 (15.79%)
Psychiatric disorders
Anxiety † 1	5/19 (26.32%)
Confusion † 1	2/19 (10.53%)
Depression † 1	5/19 (26.32%)
Insomnia † 1	4/19 (21.05%)
Mania † 1	1/19 (5.26%)
Suicidal ideation † 1	1/19 (5.26%)
Renal and urinary disorders
Acute kidney injury † 1	1/19 (5.26%)
Chronic kidney disease † 1	2/19 (10.53%)
Proteinuria † 1	1/19 (5.26%)
Renal and urinary disorders - Other, specify † 1	1/19 (5.26%)
Urinary frequency † 1	2/19 (10.53%)
Urinary retention † 1	1/19 (5.26%)
Urinary tract pain † 1	1/19 (5.26%)
Urine discoloration † 1	1/19 (5.26%)
Reproductive system and breast disorders
Dyspareunia † 1	1/19 (5.26%)
Reproductive system and breast disorders - Other, specify † 1	1/19 (5.26%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis † 1	3/19 (15.79%)
Cough † 1	7/19 (36.84%)
Dyspnea † 1	3/19 (15.79%)
Epistaxis † 1	1/19 (5.26%)
Hoarseness † 1	1/19 (5.26%)
Nasal congestion † 1	2/19 (10.53%)
Pleural effusion † 1	1/19 (5.26%)
Pneumonitis † 1	1/19 (5.26%)
Postnasal drip † 1	1/19 (5.26%)
Sore throat † 1	4/19 (21.05%)
Skin and subcutaneous tissue disorders
Alopecia † 1	4/19 (21.05%)
Erythema multiforme † 1	1/19 (5.26%)
Pain of skin † 1	1/19 (5.26%)
Pruritus † 1	2/19 (10.53%)
Rash acneiform † 1	2/19 (10.53%)
Rash maculo-papular † 1	2/19 (10.53%)
Skin/subcutaneous tissue disorders; Other, specify † 1	3/19 (15.79%)
Vascular disorders
Hypertension † 1	9/19 (47.37%)
Hypotension † 1	1/19 (5.26%)
Lymphedema † 1	1/19 (5.26%)
Thromboembolic event † 1	1/19 (5.26%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Nancy Lin, MD
• Organization: Dana-Farber Cancer Institute
• Phone: 617-632-3800
• EMail: Nancy_Lin@dfci.harvard.edu

• Responsible Party: Nancy Lin, MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT03417544
• Other Study ID Numbers: 17-546
• First Submitted: January 16, 2018
• First Posted: January 31, 2018
• Results First Submitted: February 26, 2024
• Results First Posted: May 7, 2024
• Last Update Posted: May 7, 2024