Treatment of Brain Metastases From Breast Cancer With Eribulin Mesylate

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02581839
• Collaborator: (none)
• Enrollment: 9
• Locations: 2
• Arm: 1
• Actual Duration (Months): 55.5
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Subjects are asked to take part in a clinical research study that tests Eribulin, a new drug. Eribulin is an investigational (experimental) anti-cancer agent that has not been approved by the Food and Drug Administration (FDA) for use in patients with brain metastases. Eribulin is FDA approved for use in patients with metastatic breast cancer but the effect it may or may not have on brain metastases has not been studied.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer; Brain Metastases	Drug: Eribulin Mesylate; Device: MRI; Drug: Pre-Medication: Zofran; Drug: Pre-Medication: Decadron	Phase 2

Detailed Description

Primary Objectives:

To determine the 3-month central nervous system (CNS)-progression free survival (PFS) for patients with metastatic breast cancer with brain metastases treated with eribulin mesylate.

Secondary Objective(s):

1. Estimate CNS complete and partial response rates (CR and PR) and duration of CNS response in this patient population.

2 Evaluate toxicity in patients with breast cancer with brain metastases treated with eribulin mesylate.

3 Estimate clinical benefit rate (CBR) at 3 months in breast cancer patients with brain metastases treated with eribulin mesylate. (CBR is the sum of CR, PR and stable disease at 3 months).

4 To estimate systemic disease (extra cranial) response rate and duration of systemic response in this patient population.

5 Overall survival in this patient population.

Design:

This is a phase II study that will require patients to evaluate the primary objective (CNS PFS at 3 months). Study patients will have a baseline brain MRI and a second MRI at 12 weeks to evaluate disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Brain Metastases From Breast Cancer With Eribulin Mesylate
• Actual Study Start Date: Nov 17, 2015
• Actual Primary Completion Date: Jul 2, 2018
• Actual Study Completion Date: Jul 2, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Eribulin Mesylate The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate

Drug: Eribulin Mesylate; Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.; Other Names: Halaven ; Device: MRI; An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate; Other Names: Magnetic Resonance Imaging ; Drug: Pre-Medication: Zofran; Zofran at 8mg orally. Given at the discretion of the treating physician; Drug: Pre-Medication: Decadron; decadron at 8mg orally. Given at the discretion of the treating physician

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS) [At 12 weeks]

   The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.

Secondary Outcome Measures

1. Objective Response Rate (RR) [up to 2 years from start of treatment]

   The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.

2. Median Duration of CNS Response [up to 2 years from start of treatment]

   The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.

3. Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events [up to 2 years from start of treatment]

   The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin.

4. Number of Patients With CBR [At 12 weeks]

   The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR)

5. Systemic Disease Response Rate [up to 2 years from start of treatment]

   The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population

6. Median Overall Survival (OS) [up to 2 years from start of treatment]

   The study team will generate a Kaplan-Meier curve of OS.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female with histologically confirmed breast cancer.

• Patients must have evidence of metastatic disease (non measurable disease is eligible).

• Radiologically confirmed metastatic brain lesion by MRI.

• Brain metastases from breast cancer with or without prior WBRT, STS of surgical resection. Progression must be documented in an at least one lesion untreated by SRS or in any site after surgery or WBRT.

• Patients must be neurologically stable and with stable dose steroids and anticonvulsants for at least 1 week prior to obtaining the baseline MRI of the brain, and/or at least 1 week prior to beginning study treatment.

• No presence of uncontrolled systemic disease or tumor related complication which, in opinion of the investigator, might restrict life expectancy to less than 3 months.

• Patients may not be on any cytotoxic chemotherapy or hormonal treatment for breast cancer during protocol treatment. Trastuzumab is allowed in HER2 positive patients).

• Able to comprehend and willing to sign an Informed Consent Form (ICF)

• Karnofsky performance status ≥ 60

• No brain radiation therapy > 4 weeks

• No chemotherapy for > 3 weeks before planned start of protocol treatment

• Adequate bone marrow, renal, and hepatic function, per local reference laboratory ranges as follows:

• Absolute neutrophil count (ANC) ≥ 1,500/mm3

• Platelet count ≥ 100,000/mm3

• Hemoglobin ≥ 9 g/dL

• Calculated creatinine clearance (CrCl) ≥ 30mL/min (Cockcroft-Gault method)

• Patients with normal, mild or moderate hepatic dysfunction are eligible.

• Calcium <10.1 mg/dL (corrected to serum albumin as follows: Corrected Calcium = (0.8 x (4 - patient albumin)) + serum Ca

• Females of child-bearing potential must have a negative pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy (double barrier method of birth control or abstinence) from screening through 3 months after the last dose of treatment

• Able to undergo MRI evaluation with and without gadolinium contrast

Exclusion Criteria:

• Patients with the presence of an active infection, abscess or fistula

• Known leptomeningeal disease or CNS midline shifts.

• Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease.

• Severe conduction abnormality including significant QTc prolongation >450ms.

• Patients with grade 3/4 peripheral neuropathy.

• Patients with pacemaker or an ICD devices.

• Previous treatment with eribulin mesylate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
2	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center

Investigators

• Principal Investigator: Paula Silverman, MD, University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 25, 2018

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02581839
• Other Study ID Numbers: CASE7113
• First Posted: Oct 21, 2015
• Last Update Posted: Jul 30, 2020
• Last Verified: Jul 1, 2020

• 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
• Keywords provided by Case Comprehensive Cancer Center: eribulin; central nervous system; CNS; Eribulin Mesylate; Halaven
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Dexamethasone; Dexamethasone acetate; Ondansetron; BB 1101

Study Results

Participant Flow

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Overall Participants	9
Age, Customized (Count of Participants)
20-29	0 0%
30-39	3 33.3%
40-49	0 0%
50-59	3 33.3%
60-69	1 11.1%
70-79	1 11.1%
80-89	1 11.1%
Sex: Female, Male (Count of Participants)
Female	9 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	9 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 11.1%
White	7 77.8%
More than one race	0 0%
Unknown or Not Reported	1 11.1%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS)
Description	The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time Frame	At 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	9
Number (95% Confidence Interval) [percentage of participants]	88.9 987.8%

2. Secondary Outcome

Title	Objective Response Rate (RR)
Description	The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time Frame	up to 2 years from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	9
Number [percentage of participants]	11.1 123.3%

3. Secondary Outcome

Title	Median Duration of CNS Response
Description	The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time Frame	up to 2 years from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	9
Median (Full Range) [weeks]	22.6

4. Secondary Outcome

Title	Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events
Description	The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin.
Time Frame	up to 2 years from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	9
Count of Participants [Participants]	3 33.3%

5. Secondary Outcome

Title	Number of Patients With CBR
Description	The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR)
Time Frame	At 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	9
Count of Participants [Participants]	5 55.6%

6. Secondary Outcome

Title	Systemic Disease Response Rate
Description	The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population
Time Frame	up to 2 years from start of treatment

Outcome Measure Data

Analysis Population Description

Data not collected due to too few participants on study for a significant length of time

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	0

7. Secondary Outcome

Title	Median Overall Survival (OS)
Description	The study team will generate a Kaplan-Meier curve of OS.
Time Frame	up to 2 years from start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Measure Participants	9
Median (Full Range) [months]	15.7

Adverse Events

Time Frame	30 days after treatment has been discontinued, an average of 5 months
Arm/Group Title	Eribulin Mesylate
Arm/Group Description	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
All Cause Mortality
	Eribulin Mesylate
	Affected / at Risk (%)	# Events
Total	7/9 (77.8%)
Serious Adverse Events
	Eribulin Mesylate
	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	1/9 (11.1%)	1
General disorders
Fatigue	1/9 (11.1%)	1
Infections and infestations
Lung infection	1/9 (11.1%)	1
Investigations
Neutrophil count decreased	1/9 (11.1%)	2
Platelet count decreased	1/9 (11.1%)	1
White blood cell decreased	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	1/9 (11.1%)	1
Nervous system disorders
worsening pseudomeningeocele	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/9 (11.1%)	1
Vascular disorders
Thromboembolic event	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Eribulin Mesylate
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Anemia	6/9 (66.7%)	11
Cardiac disorders
Palpitations	1/9 (11.1%)	1
Eye disorders
Blurred vision	1/9 (11.1%)	1
Dry eye	1/9 (11.1%)	1
Aura	1/9 (11.1%)	1
Neuro; Other- perception/focus	1/9 (11.1%)	1
Vision Change	1/9 (11.1%)	1
Gastrointestinal disorders
Ascites	1/9 (11.1%)	3
Constipation	6/9 (66.7%)	8
Diarrhea	4/9 (44.4%)	12
Dry mouth	2/9 (22.2%)	2
Dyspepsia	1/9 (11.1%)	1
Mucositis oral	3/9 (33.3%)	6
Nausea	5/9 (55.6%)	9
Oral pain	1/9 (11.1%)	1
Vomiting	2/9 (22.2%)	3
General disorders
Edema face	1/9 (11.1%)	2
Edema limbs	3/9 (33.3%)	6
Fatigue	8/9 (88.9%)	27
Fever	1/9 (11.1%)	1
Gait disturbance	2/9 (22.2%)	2
Malaise	2/9 (22.2%)	2
Non-cardiac chest pain	2/9 (22.2%)	2
Pain	1/9 (11.1%)	1
Infections and infestations
Lung infection	1/9 (11.1%)	1
Rhinitis infective	1/9 (11.1%)	1
Sinusitis	1/9 (11.1%)	1
Upper respiratory infection	1/9 (11.1%)	2
Urinary tract infection	1/9 (11.1%)	2
Injury, poisoning and procedural complications
Fall	2/9 (22.2%)	2
Investigations
Alanine aminotransferase increased	3/9 (33.3%)	6
Alkaline phosphatase increased	2/9 (22.2%)	2
Aspartate aminotransferase increased	2/9 (22.2%)	4
Blood bilirubin increased	1/9 (11.1%)	1
Creatinine increased	1/9 (11.1%)	2
Lymphocyte count decreased	5/9 (55.6%)	20
Neutrophil count decreased	3/9 (33.3%)	6
Platelet count decreased	4/9 (44.4%)	6
White blood cell decreased	6/9 (66.7%)	16
Metabolism and nutrition disorders
Anorexia	2/9 (22.2%)	3
Dehydration	1/9 (11.1%)	1
Hyperglycemia	3/9 (33.3%)	3
Hypernatremia	1/9 (11.1%)	1
Hypoalbuminemia	2/9 (22.2%)	3
Hypocalcemia	2/9 (22.2%)	5
Hypokalemia	1/9 (11.1%)	2
Hypomagnesemia	2/9 (22.2%)	4
Hyponatremia	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Chest wall pain	1/9 (11.1%)	3
Generalized muscle weakness	2/9 (22.2%)	10
Joint range motion decreased	1/9 (11.1%)	1
Lock jaw	1/9 (11.1%)	1
Pain in extremity	4/9 (44.4%)	4
Nervous system disorders
Ataxia	1/9 (11.1%)	1
Dizziness	4/9 (44.4%)	4
Dysgeusia	3/9 (33.3%)	6
Headache	2/9 (22.2%)	6
Memory impairment	3/9 (33.3%)	4
L carpel tunnel	1/9 (11.1%)	1
woozy feeling	1/9 (11.1%)	1
Oculomotor nerve disorder	1/9 (11.1%)	3
Peripheral motor neuropathy	2/9 (22.2%)	2
Peripheral sensory neuropathy	4/9 (44.4%)	4
Recurrent laryngeal nerve palsy	1/9 (11.1%)	1
Psychiatric disorders
Insomnia	3/9 (33.3%)	3
Renal and urinary disorders
Acute kidney injury	1/9 (11.1%)	1
Chronic kidney disease	1/9 (11.1%)	1
Urinary frequency	1/9 (11.1%)	1
Urinary urgency	1/9 (11.1%)	1
Reproductive system and breast disorders
Pelvic pain	1/9 (11.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	3/9 (33.3%)	3
Dyspnea	4/9 (44.4%)	7
Epistaxis	1/9 (11.1%)	2
Hoarseness	2/9 (22.2%)	2
Nasal congestion	2/9 (22.2%)	2
Pleural effusion	1/9 (11.1%)	2
Productive cough	1/9 (11.1%)	1
Sore throat	2/9 (22.2%)	2
Wheezing	1/9 (11.1%)	2
Skin and subcutaneous tissue disorders
Alopecia	4/9 (44.4%)	6
Dry skin	2/9 (22.2%)	2
Hyperhidrosis	1/9 (11.1%)	1
Pruritus	1/9 (11.1%)	1
Rash maculo-papular	2/9 (22.2%)	2
folliculitis	1/9 (11.1%)	1
Vascular disorders
Hypertension	3/9 (33.3%)	4
Hypotension	1/9 (11.1%)	2
Lymphedema	2/9 (22.2%)	2
Thromboembolic event	2/9 (22.2%)	3
Deep vein thrombosis	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.