Single Arm on the Tolerability of Weekly Nab-paclitaxel

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01702844
• Collaborator: Celgene (Industry)
• Enrollment: 42
• Locations: 8
• Arm: 1
• Actual Duration (Months): 72.5
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of weekly nab-paclitaxel for a second-line treatment in elderly subjects, 70 years of age or greater, with non-small cell lung cancer (NSCLC)

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer (NSCLC)	Drug: Nab-Paclitaxel	Phase 2

Detailed Description

This will be a non-randomized phase II study evaluating the safety and efficacy of weekly nab-paclitaxel for second-line treatment in 42 elderly patients, who are 70 years of age or greater with non-small cell lung cancer (NSLC). Patients will be required to have progressed on a single prior regimen. Nab-paclitaxel 100mg/m2 will be administered intravenously, weekly for 3 weeks of every 4-week cycle. After every two cycles of therapy, imaging will be performed to assess for response. Patients will be eligible to continue receiving therapy until the time of disease progression.

Primary Objectives To evaluate the tolerability of weekly nab-paclitaxel in older adults with advanced lung cancer who have progressed on at least 1 prior regimen after 6 cycles or 3 weeks after discontinuation of treatment, for those who come off treatment earlier.

Secondary Objectives To estimate overall survival To estimate progression-free survival To estimate the response rate

Correlative Objectives To explore baseline components of the Geriatric Assessment (GA) as predictors of chemotherapy tolerance and overall survival To explore the use of p16 measurements in the elderly as predictors of chemotherapy tolerance and overall survival To explore the impact of weekly nab-paclitaxel treatment on quality of life, as measured by Lung Cancer Symptom Scale (LCSS) and Functional Assessment of Cancer Therapy-Lung (FACT-L).

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LCCC 1210 - Phase II, Multicenter, Single Arm Study of the Tolerability of Weekly Nab-paclitaxel as Second Line Treatment for Elderly Patients With Advanced Lung Cancer
• Actual Study Start Date: Jun 25, 2013
• Actual Primary Completion Date: Jun 23, 2017
• Actual Study Completion Date: Jul 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nab paclitaxel Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle	Drug: Nab-Paclitaxel; Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15; Other Names: Abraxane

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Without Any Adverse Events Grade 3 or Higher [168 days after start of treatment (6 cycles) (or 3 weeks after discontinuation of treatment, for those who come off treatment earlier)]

   Tolerability of weekly nab-paclitaxel, as measured by occurrence of Grade 3 or worse toxicity after 6 cycles or 3 weeks after discontinuation of treatment, for those who came off treatment earlier as measured by the NCI Common Terminology Criteria for Adverse Events CTCAE, version 4. The CTCAE is a descriptive terminology utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Secondary Outcome Measures

1. Median Overall Survival [up to 2 years after end of treatment (treatment lasts up to 168 days (up to 6 cycles of 28 days each))]

   Overall Survival is defined as the time from day 1 (D1) of treatment until death as a result of any cause

2. Median Progression Free Survival [up to 2 years after end of treatment (treatment lasts up to 168 days (up to 6 cycles of 28 days each))]

   Progression free survival is defined as the time from D1 of treatment until progression or death as a result of any cause. Progressive Disease (PD) is determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. PD is at least a 20% increase in the sum of the longest diameters (LD) of the target lesions taking as reference the smallest sum LD recorded since the treatment started including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of one or more new lesions also constitutes PD.

3. Overall Response Rate [168 days after start of treatment (6 cycles) (or 3 weeks after discontinuation of treatment, for those who come off treatment earlier)]

   Response will be measured by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. The Overall Response rate is defined as the percentage of participants with CR or PR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 70 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed written informed consent

• Male or female patient

• Greater than or equal to 70 years of age

• Diagnosis of NSCLC histologically or cytologically confirmed

• Internal Association for the Study of Lung Cancer Version 7 Stage IV disease or recurrence after prior surgery or radiotherapy

• Progression following one line of prior chemotherapy consisting of a platinum agent plus a standard cytotoxic partner agent other than a taxane, typically pemetrexed gemcitabine or vinorelbine

• A single agent non cytoxic regimen if the patient has a molecular change that the non cytotoxic regimen would be expected to be efficacious for epidermal growth factor receptor (EGFR) mutation for erlotinib and (EML4) anaplastic lymphoma kinase (ALk) or ROS1 for crizotinib

• Eastern Cooperative Oncology Group performance status 0 to 2

• Adequate organ and bone marrow function as defined by

• Absolute neutrophil count greater than or equal to 1500 cells/mm3

• Creatinine less than or equal to 1.5 mg dL

• Total bilirubin less than or equal to 1.5 mg dL

• Alkaline phosphatase less than or equal to 2.5 x upper limit of normal

• Alanine aminotransferase less than or equal to 2.5 x upper limit of normal

• Aspartate aminotransferase less than or equal to 2.5 upper limit of normal

• Recovered from all reversible toxicities related to their previous treatment to less than or equal to grade 1 or baseline

• Patients must have equal to grade 2 pre existing peripheral neuropathy

• Women of childbearing potential and sexually active men must agree to use effective contraception prior to study entry for the duration of study participation and for three months after completing treatment. Adequate contraception is defined as any medically recommended method as per standard of care

• Negative serum or urine bhCG pregnancy test at screening for patients of childbearing potential

• Patients with brain metastases may participate if they have undergone appropriate treatment for the lesions are at least two weeks post treatment without evidence for post treatment progression have no significant neurologic symptoms and no longer require steroids for the reason of brain metastases. Patients with symptoms suggestive of central nervous system (CNS) metastases should be evaluated with imaging prior to study participation

Exclusion Criteria:

• Prior taxane therapy for any indication

• Less than 3 weeks elapsed since prior exposure to chemotherapy

• Pre existing neuropathy greater than grade 1

• Other active invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years localized squamous cell carcinoma of the skin basal cell carcinoma of the skin, carcinoma in situ of teh cervix or other malignancies requiring locally ablative therapy only will not result in exclusion

• Concomitant anticancer therapy immunotherapy or radiation therapy within prior 4 weeks

• Have received treatment within the last 30 days prior to study entry with any drug that has not receive regulatory approval for an indication at the time of study entry

• Uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring IV antibiotics symptomatic congestive heart failure unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements

• Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of nab paclitaxel because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study

• Known hypersensitivity to protein bound paclitaxel

• Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
3	Rex Healthcare	Raleigh	North Carolina	United States	27607
4	Cleveland Clinic	Cleveland	Ohio	United States	44195
5	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
6	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
7	Bon Secours Virginia Health System	Midlothian	Virginia	United States	23114
8	Swedish Cancer Institute	Seattle	Washington	United States	98104

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• Celgene

Investigators

• Principal Investigator: Jared Weiss, MD, UNC Lineberger Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 26, 2017

More Information

Additional Information:

• Lineberger Comprehensive Cancer Center homepage
• National Cancer Institute (NCI) homepage

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01702844
• Other Study ID Numbers: LCCC 1210
• First Posted: Oct 8, 2012
• Last Update Posted: Oct 8, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by UNC Lineberger Comprehensive Cancer Center: Nab paclitaxel; Abraxane; First Line; Non small cell lung cancer; NSCLC; Phase II; Non-Randomized; Elderly; Lineberger; UNC; LCCC 1210
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel

Study Results

Participant Flow

Recruitment Details	A total of 42 participants were accrued between June 2013 and April 2017 at 7 institutions in the United States
Pre-assignment Detail	Another 9 participants signed consent but did not start the trial due to screen failure (6), progression of disease prior to study start (1) and withdrawal of consent prior to start (2.)

Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
Period Title: Overall Study
STARTED	42
Disease Progression	23
COMPLETED	23
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
Overall Participants	42
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	76.3
Sex: Female, Male (Count of Participants)
Female	22 52.4%
Male	20 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.4%
Not Hispanic or Latino	41 97.6%
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	7 16.7%
White	35 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	42 100%
Smoking status (Count of Participants)
Never smoker	4 9.5%
Former/current smoker	38 90.5%
Performance status (Count of Participants)
0, Fully active	5 11.9%
1, Restricted in strenuous activity but ambulatory	28 66.7%
2, limited selfcare	9 21.4%
Exercise (Count of Participants)
Never	10 23.8%
Few times per month	3 7.1%
1-2 times per week	6 14.3%
3-4 times per week	2 4.8%
More than or equal to 5 times per week	1 2.4%
Unknown/Not reported	20 47.6%
Alcohol (Count of Participants)
No	13 31%
Yes	7 16.7%
Almost never	7 16.7%
Unknown/Not reported	15 35.7%
Histology (Count of Participants)
Adenocarcinoma	35 83.3%
Squamous cell carcinoma	7 16.7%
Prior treatment regimens (Count of Participants)
Carboplatin plus pemetrexed	26 61.9%
Carboplatin, pemetrexed, and bevacizumab	4 9.5%
Cisplatin plus pemetrexed	1 2.4%
Carboplatin plus gemcitabine	11 26.2%
Nivolumab	8 19%
Erlotinib	1 2.4%
Other prior regimens	3 7.1%
Best response to prior therapies (Count of Participants)
Complete response	0 0%
Partial response	3 7.1%
Stable disease	16 38.1%
Progressive disease	22 52.4%
Unknown/Not evaluable	13 31%
Frailty index (Count of Participants)
Robust (0 to <0.2)	5 11.9%
Prefrail (0.2-0.35)	10 23.8%
Frail (>0.35)	11 26.2%
Unknown/Not assessed	16 38.1%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Without Any Adverse Events Grade 3 or Higher
Description	Tolerability of weekly nab-paclitaxel, as measured by occurrence of Grade 3 or worse toxicity after 6 cycles or 3 weeks after discontinuation of treatment, for those who came off treatment earlier as measured by the NCI Common Terminology Criteria for Adverse Events CTCAE, version 4. The CTCAE is a descriptive terminology utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time Frame	168 days after start of treatment (6 cycles) (or 3 weeks after discontinuation of treatment, for those who come off treatment earlier)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
Measure Participants	42
Count of Participants [Participants]	28 66.7%

2. Secondary Outcome

Title	Median Overall Survival
Description	Overall Survival is defined as the time from day 1 (D1) of treatment until death as a result of any cause
Time Frame	up to 2 years after end of treatment (treatment lasts up to 168 days (up to 6 cycles of 28 days each))

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
Measure Participants	42
Median (95% Confidence Interval) [Months]	9.3

3. Secondary Outcome

Title	Median Progression Free Survival
Description	Progression free survival is defined as the time from D1 of treatment until progression or death as a result of any cause. Progressive Disease (PD) is determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. PD is at least a 20% increase in the sum of the longest diameters (LD) of the target lesions taking as reference the smallest sum LD recorded since the treatment started including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of one or more new lesions also constitutes PD.
Time Frame	up to 2 years after end of treatment (treatment lasts up to 168 days (up to 6 cycles of 28 days each))

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
Measure Participants	42
Median (95% Confidence Interval) [Months]	5.2

4. Secondary Outcome

Title	Overall Response Rate
Description	Response will be measured by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. The Overall Response rate is defined as the percentage of participants with CR or PR
Time Frame	168 days after start of treatment (6 cycles) (or 3 weeks after discontinuation of treatment, for those who come off treatment earlier)

Outcome Measure Data

Analysis Population Description

4 subjects were not analyzed for this outcome due to lack of follow up disease assessments (off treatment after only one cycle for hospice and/or death)

Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
Measure Participants	38
Number (95% Confidence Interval) [percentage of patients with response]	34.2

Adverse Events

Time Frame	From day 1 of study treatment to 30 days after treatment is discontinued (with an average treatment duration of 168 days)
Arm/Group Title	Nab Paclitaxel
Arm/Group Description	Patients will receive nab-paclitaxel once weekly for 3 weeks of every 4 week cycle Nab-Paclitaxel: Administer 2 cycles of Nab-Paclitaxel 100 mg/m2 IV on days 1 8 and 15
All Cause Mortality
	Nab Paclitaxel
	Affected / at Risk (%)	# Events
Total	41/42 (97.6%)
Serious Adverse Events
	Nab Paclitaxel
	Affected / at Risk (%)	# Events
Total	15/42 (35.7%)
Blood and lymphatic system disorders
Anemia	1/42 (2.4%)
Cardiac disorders
Atrioventricular block complete	1/42 (2.4%)
Heart failure	1/42 (2.4%)
Myocardial infarction	1/42 (2.4%)
Pericardial effusion	1/42 (2.4%)
General disorders
Chills	1/42 (2.4%)
Fever	1/42 (2.4%)
Gait disturbance	1/42 (2.4%)
Infections and infestations
Bronchial infection	1/42 (2.4%)
Infections and infestations - Other, specify	1/42 (2.4%)
Sepsis	1/42 (2.4%)
Investigations
White blood cell decreased	1/42 (2.4%)
Metabolism and nutrition disorders
Hypocalcemia	1/42 (2.4%)
Hypophosphatemia	1/42 (2.4%)
Nervous system disorders
Stroke	1/42 (2.4%)
Psychiatric disorders
Confusion	1/42 (2.4%)
Renal and urinary disorders
Acute kidney injury	1/42 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/42 (4.8%)
Pleural effusion	1/42 (2.4%)
Pneumonitis	1/42 (2.4%)
Vascular disorders
Hypertension	1/42 (2.4%)
Vasculitis	1/42 (2.4%)
Other (Not Including Serious) Adverse Events
	Nab Paclitaxel
	Affected / at Risk (%)	# Events
Total	41/42 (97.6%)
Blood and lymphatic system disorders
Anemia	18/42 (42.9%)
Blood and lymphatic system	1/42 (2.4%)
Febrile neutropenia	1/42 (2.4%)
Cardiac disorders
Cardiac disorders - Other,	1/42 (2.4%)
Sinus tachycardia	2/42 (4.8%)
Supraventricular tachycard	1/42 (2.4%)
Ear and labyrinth disorders
Vertigo	1/42 (2.4%)
Endocrine disorders
Endocrine disorders - Othe	1/42 (2.4%)
Eye disorders
Blurred vision	1/42 (2.4%)
Eye disorders - Other, spe	2/42 (4.8%)
Retinal vascular disorder	1/42 (2.4%)
Watering eyes	2/42 (4.8%)
Gastrointestinal disorders
Abdominal pain	5/42 (11.9%)
Anal hemorrhage	1/42 (2.4%)
Constipation	11/42 (26.2%)
Diarrhea	8/42 (19%)
Dry mouth	2/42 (4.8%)
Dyspepsia	1/42 (2.4%)
Dysphagia	1/42 (2.4%)
Flatulence	1/42 (2.4%)
Mucositis oral	4/42 (9.5%)
Nausea	12/42 (28.6%)
Vomiting	7/42 (16.7%)
General disorders
Edema limbs	16/42 (38.1%)
Fatigue	26/42 (61.9%)
Fever	3/42 (7.1%)
General disorders and admi	1/42 (2.4%)
Infusion site extravasatio	1/42 (2.4%)
Non-cardiac chest pain	1/42 (2.4%)
Pain	4/42 (9.5%)
Infections and infestations
Bronchial infection	2/42 (4.8%)
Mucosal infection	5/42 (11.9%)
Nail infection	1/42 (2.4%)
Paronychia	2/42 (4.8%)
Sinusitis	1/42 (2.4%)
Skin infection	4/42 (9.5%)
Upper respiratory infectio	6/42 (14.3%)
Urinary tract infection	1/42 (2.4%)
Injury, poisoning and procedural complications
Fall	2/42 (4.8%)
Fracture	1/42 (2.4%)
Investigations
Alanine aminotransferase i	1/42 (2.4%)
Alkaline phosphatase incre	3/42 (7.1%)
Aspartate aminotransferase	4/42 (9.5%)
Blood bilirubin increased	1/42 (2.4%)
Creatinine increased	3/42 (7.1%)
Lymphocyte count decreased	8/42 (19%)
Neutrophil count decreased	15/42 (35.7%)
Platelet count decreased	4/42 (9.5%)
Weight gain	1/42 (2.4%)
Weight loss	2/42 (4.8%)
White blood cell decreased	16/42 (38.1%)
Metabolism and nutrition disorders
Anorexia	8/42 (19%)
Dehydration	1/42 (2.4%)
Hypercalcemia	3/42 (7.1%)
Hyperglycemia	8/42 (19%)
Hyperkalemia	3/42 (7.1%)
Hypermagnesemia	3/42 (7.1%)
Hypoalbuminemia	7/42 (16.7%)
Hypocalcemia	3/42 (7.1%)
Hypoglycemia	1/42 (2.4%)
Hypokalemia	3/42 (7.1%)
Hypomagnesemia	8/42 (19%)
Hyponatremia	3/42 (7.1%)
Hypophosphatemia	3/42 (7.1%)
Metabolism and nutrition d	1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/42 (7.1%)
Arthritis	1/42 (2.4%)
Back pain	2/42 (4.8%)
Bone pain	2/42 (4.8%)
Chest wall pain	2/42 (4.8%)
Flank pain	1/42 (2.4%)
Generalized muscle weaknes	3/42 (7.1%)
Muscle weakness lower limb	1/42 (2.4%)
Myalgia	5/42 (11.9%)
Pain in extremity	4/42 (9.5%)
Nervous system disorders
Dizziness	3/42 (7.1%)
Dysarthria	1/42 (2.4%)
Dysgeusia	3/42 (7.1%)
Headache	5/42 (11.9%)
Paresthesia	2/42 (4.8%)
Peripheral motor neuropath	4/42 (9.5%)
Peripheral sensory neuropa	20/42 (47.6%)
Presyncope	1/42 (2.4%)
Seizure	1/42 (2.4%)
Syncope	1/42 (2.4%)
Transient ischemic attacks	1/42 (2.4%)
Tremor	1/42 (2.4%)
Psychiatric disorders
Confusion	1/42 (2.4%)
Depression	2/42 (4.8%)
Insomnia	2/42 (4.8%)
Renal and urinary disorders
Acute kidney injury	2/42 (4.8%)
Renal and urinary disorder	1/42 (2.4%)
Urinary frequency	1/42 (2.4%)
Urinary incontinence	1/42 (2.4%)
Urinary tract pain	1/42 (2.4%)
Reproductive system and breast disorders
Genital edema	1/42 (2.4%)
Respiratory, thoracic and mediastinal disorders
Cough	6/42 (14.3%)
Dyspnea	8/42 (19%)
Epistaxis	1/42 (2.4%)
Hoarseness	1/42 (2.4%)
Hypoxia	1/42 (2.4%)
Nasal congestion	1/42 (2.4%)
Pneumonitis	1/42 (2.4%)
Postnasal drip	1/42 (2.4%)
Productive cough	5/42 (11.9%)
Respiratory, thoracic and	1/42 (2.4%)
Sinus disorder	1/42 (2.4%)
Skin and subcutaneous tissue disorders
Alopecia	12/42 (28.6%)
Erythema multiforme	1/42 (2.4%)
Hyperhidrosis	2/42 (4.8%)
Nail discoloration	1/42 (2.4%)
Pain of skin	1/42 (2.4%)
Photosensitivity	1/42 (2.4%)
Pruritus	1/42 (2.4%)
Rash acneiform	1/42 (2.4%)
Rash maculo-papular	2/42 (4.8%)
Scalp pain	1/42 (2.4%)
Skin hyperpigmentation	1/42 (2.4%)
Vascular disorders
Hot flashes	2/42 (4.8%)
Hypertension	2/42 (4.8%)
Hypotension	5/42 (11.9%)
Thromboembolic event	2/42 (4.8%)
Vasculitis	1/42 (2.4%)

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.