Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00859937
• Collaborator: (none)
• Enrollment: 55
• Locations: 34
• Arm: 1
• Patients Per Site: 1.6

Study Details

Study Description

Brief Summary

This phase II trial is studying how well dasatinib works in treating patients with malignant salivary gland tumors that have come back after treatment or have spread to other parts of the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Malignant Salivary Gland Neoplasm; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IV Major Salivary Gland Cancer AJCC v7	Drug: Dasatinib; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the objective response rate (complete response plus partial response) of dasatinib in adenoid cystic carcinoma (ACC).

2. Determine the progression-free survival of dasatinib in ACC.

SECONDARY OBJECTIVES:

1. Determine the duration of response. II. Determine the stable disease rate and duration of stable disease. III. Determine progression-free survival. IV. Determine the median survival.
2. Determine the overall survival. VI. Determine the safety and tolerability.

TERTIARY OBJECTIVES:

1. To examine biomarkers that relate to SRC proto-oncogene, non-receptor tyrosine kinase (Src) signal transduction and to correlate these biomarkers with clinical response to dasatinib in ACC and non-ACC malignant salivary gland tumors (MSGT).

2. Determine if activating mutations in platelet-derived growth factor alpha polypeptide (PDGFA) and KIT are associated with response in ACC.

OUTLINE:

Patients receive dasatinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed at 8 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-adenoid Cystic Malignant Salivary Tumors
• Actual Study Start Date: Mar 16, 2009
• Actual Primary Completion Date: Jan 30, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Dasatinib; Given PO; Other Names: BMS-354825 Sprycel ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Response Rate [Up to 2 months]

   Response rate is percentage of the best overall response which recoded from the start of the treatment until diseases progression/recurrence. Response criteria are defined using the international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee: Complete Response, Disappearance of all target lesions; Partial Response, >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

2. Progression-free Survival [up to 5 years]

   Progression-free survival from start of treatment to the time of disease progression or death from any cause was estimated using the Kaplan-Meier method.

Secondary Outcome Measures

1. Overall Survival [Up to 5 years]

   Kaplan-Meier curves will be generated and 90% confidence intervals will be derived.

2. Changes in Laboratory Correlates [Baseline and 4 weeks]

   Changes in laboratory correlates pre-post therapy will be analyzed using paired t-tests. The association between RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorp response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as cova only due to the small sample size) in a Cox regression model of progression-free survival.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed malignant salivary gland tumor (MSGT), including one of the following histologic subtypes:

• Adenoid cystic carcinoma (ACC) with c v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit) overexpression or non-ACC MSGT that is not amenable to potentially curable surgery or radiation

• c-KIT overexpression in ACC patients is defined as cluster of differentiation (CD) 117 staining by immunohistochemistry (IHC) in 25% of tumor cells

• No stipulation for c-KIT overexpression is not required for non-ACC MSGT patients

• Patients must have radiographically measurable disease; radiographically measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan

• Patients must have evidence of disease progression (objective growth of existing tumors) within 4 months of study entry

• No known brain metastases, unless patient meets both of the following criteria:

• Neurologic status stable for >= 8 weeks after completion of definitive local therapy (surgery or radiotherapy)

• No neurologic dysfunction that would confound study results

• Life expectancy greater than 12 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 OR Karnofsky performance status (PS) >= 60%

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelet >= 100,000/mcL

• Hemoglobin >= 9 g/dL

• Serum calcium =< 12.0 mg/dL

• Total serum bilirubin within normal institutional limits

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; all women of childbearing potential must have a negative pregnancy test prior to receiving dasatinib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery

• Patients may not be receiving any other investigational agents

• No prior treatment with any other targeted agents that inhibit vascular endothelial growth factor receptor (VEGFR), Breakpoint cluster region (BCR) ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL), c-Src, c-KIT, platelet-derived growth factor (PDGF) beta receptor, or ephrin type-A receptor 2 (EPHA2) (e.g., imatinib mesylate)

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib

• Patients with corrected QT interval (QTc) prolongation (defined as a QTc interval equal to or greater than 500 msec), serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia greater than or equal to 3 beats in a row) or other significant echocardiogram (ECG) abnormalities are excluded

• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for intravenous [IV] alimentation, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded

• Patients with any of the following conditions are excluded:

• Serious or non-healing wound, ulcer, or bone fracture

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses within the past 28 days

• Any history of cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months

• History of myocardial infraction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 6 months

• History of pulmonary embolism within the past 12 months

• Ejection fraction less than institutional normal by echocardiograph (only required for patients with a known history of congestive heart failure, low ejection fraction, or clinical symptoms/findings consistent with congestive heart failure)

• Patients taking medications that are potent inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme will be determined following a review of their case by the Principal Investigator; every effort should be made to switch patients taking such agents or substances to other medications

• Patients with known brain metastases should be excluded; patients with brain metastases with stable neurologic status following local therapy (surgery or radiation) for at least 8 weeks from definitive therapy and without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events are eligible for participation; patients cannot be receiving enzyme inducing anti-convulsants including carbamazepine, phenobarbital, and phenytoin

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible

• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dasatinib

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

• Patients who have an active pleural or pericardial effusion of any grade

• Diagnosis of any second malignancy within the last 5 years; basal cell carcinoma, squamous cell skin cancer, stage I carcinoma fully treated, or in situ carcinoma that have been adequately treated with no evidence of recurrent disease for 12 months will be eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211-1850
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
3	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	Mercy UC Davis Cancer Center	Merced	California	United States	95340
5	Moffitt Cancer Center	Tampa	Florida	United States	33612
6	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
7	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
8	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
9	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
10	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
11	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
12	Loyola University Medical Center	Maywood	Illinois	United States	60153
13	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
14	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
15	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
16	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
17	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
18	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
19	Oncology Care Associates PLLC	Saint Joseph	Michigan	United States	49085
20	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
21	Montefiore Medical Center-Wakefield Campus	Bronx	New York	United States	10466
22	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
23	Mount Sinai Hospital	New York	New York	United States	10029
24	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
25	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
26	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
27	Medical University of South Carolina	Charleston	South Carolina	United States	29425
28	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
29	M D Anderson Cancer Center	Houston	Texas	United States	77030
30	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
31	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
32	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
33	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
34	CHUM-Hotel Dieu de Montreal	Montreal	Quebec	Canada	H2W 1T8

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stuart Wong, University of Chicago Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00859937
• Other Study ID Numbers: NCI-2009-01165; NCI-2009-01165; CDR0000636685; UCCRC-16691B; 16691B; 8271; N01CM00032; N01CM00038; N01CM00071; P30CA014599
• First Posted: Mar 11, 2009
• Last Update Posted: Apr 20, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Carcinoma; Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic; Recurrence; Dasatinib

Study Results

Participant Flow

Arm/Group Title	Adenoid Cystic Carcinoma	Non Adenoid Cystic Carcinoma
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	41	14
COMPLETED	40	14
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Adenoid Cystic Carcinoma	Non Adenoid Cystic Carcinoma	Total
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	40	14	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56	56	56
Sex: Female, Male (Count of Participants)
Female	22 55%	4 28.6%	26 48.1%
Male	18 45%	10 71.4%	28 51.9%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Response rate is percentage of the best overall response which recoded from the start of the treatment until diseases progression/recurrence. Response criteria are defined using the international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee: Complete Response, Disappearance of all target lesions; Partial Response, >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.
Time Frame	Up to 2 months

Outcome Measure Data

Analysis Population Description

There are two subtype cohorts, adenoid cystic carcinoma and non adenoid cystic carcinoma of malignant salivary gland tumors, with the same treatment. The two groups were analyzed separately and therefore no comparisons are made between the two groups.

Arm/Group Title	Adenoid Cystic Carcinoma	Non Adenoid Cystic Carcinoma
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	40	14
Complete response	0 0%	0 0%
Partial response	1 2.5%	0 0%
Stable disease	20 50%	7 50%
Progressive disease	12 30%	4 28.6%
Other	7 17.5%	3 21.4%

2. Primary Outcome

Title	Progression-free Survival
Description	Progression-free survival from start of treatment to the time of disease progression or death from any cause was estimated using the Kaplan-Meier method.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

There are two subtype cohorts, adenoid cystic carcinoma and non adenoid cystic carcinoma of malignant salivary gland tumors, with the same treatment. The two groups were analyzed separately and therefore no comparisons are made between the two groups.

Arm/Group Title	Adenoid Cystic Carcinoma	Non Adenoid Cystic Carcinoma
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	40	14
Median (90% Confidence Interval) [months]	4.8	2.7

3. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier curves will be generated and 90% confidence intervals will be derived.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

There are two subtype cohorts, adenoid cystic carcinoma and non adenoid cystic carcinoma of malignant salivary gland tumors, with the same treatment. The two groups were analyzed separately and therefore no comparisons are made between the two groups.

Arm/Group Title	Adenoid Cystic Carcinoma	Non Adenoid Cystic Carcinoma
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	40	14
Median (90% Confidence Interval) [months]	14.5	4.8

4. Secondary Outcome

Title	Changes in Laboratory Correlates
Description	Changes in laboratory correlates pre-post therapy will be analyzed using paired t-tests. The association between RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorp response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as cova only due to the small sample size) in a Cox regression model of progression-free survival.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Biomarkers not done due to insufficient clinical responses thus making the biomarker analysis scientifically untenable.

Arm/Group Title	Adenoid Cystic Carcinoma	Non Adenoid Cystic Carcinoma
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 5 years
Adverse Event Reporting Description	All serious adverse events were reported. Other adverse events occurring in ≥5% of the study subjects were reported.
Arm/Group Title	Adenoid Cystic Carcinoma		Non Adenoid Cystic Carcinoma
Arm/Group Description	Patients with Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.		Patients with non Adenoid cystic carcinoma of malignant salivary gland tumors receive oral dasatinib (70mg) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Adenoid Cystic Carcinoma		Non Adenoid Cystic Carcinoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Adenoid Cystic Carcinoma		Non Adenoid Cystic Carcinoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/40 (30%)		8/14 (57.1%)
Cardiac disorders
Chest pain	0/40 (0%)		1/14 (7.1%)
Eye disorders
Loss of vision	1/40 (2.5%)		0/14 (0%)
Gastrointestinal disorders
Dysphagia	0/40 (0%)		1/14 (7.1%)
Nausea	1/40 (2.5%)		0/14 (0%)
General disorders
Non-cardiac chest pain	0/40 (0%)		1/14 (7.1%)
Infections and infestations
Infections and infestations	1/40 (2.5%)		0/14 (0%)
Investigations
Alanine aminotransferase increased	1/40 (2.5%)		0/14 (0%)
Metabolism and nutrition disorders
Anorexia	1/40 (2.5%)		1/14 (7.1%)
Hyperglycemia	1/40 (2.5%)		0/14 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death	2/40 (5%)		1/14 (7.1%)
Nervous system disorders
Cauda equina syndrome	1/40 (2.5%)		0/14 (0%)
Psychiatric disorders
Confusion	0/40 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/40 (7.5%)		1/14 (7.1%)
Hypoxia	0/40 (0%)		1/14 (7.1%)
Pleural effusion	1/40 (2.5%)		0/14 (0%)
Pneumonitis	1/40 (2.5%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Urticaria	1/40 (2.5%)		0/14 (0%)
Vascular disorders
Thromboembolic event	0/40 (0%)		1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	Adenoid Cystic Carcinoma		Non Adenoid Cystic Carcinoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/40 (97.5%)		13/14 (92.9%)
Blood and lymphatic system disorders
Anemia	20/40 (50%)		5/14 (35.7%)
Lymph node pain	0/40 (0%)		1/14 (7.1%)
Cardiac disorders
Palpitations	0/40 (0%)		1/14 (7.1%)
Ear and labyrinth disorders
Ear pain	2/40 (5%)		0/14 (0%)
Gastrointestinal disorders
Abdominal distension	0/40 (0%)		1/14 (7.1%)
Constipation	11/40 (27.5%)		1/14 (7.1%)
Diarrhea	13/40 (32.5%)		6/14 (42.9%)
Dry mouth	1/40 (2.5%)		1/14 (7.1%)
Dyspepsia	2/40 (5%)		0/14 (0%)
Dysphagia	4/40 (10%)		1/14 (7.1%)
Eructation	0/40 (0%)		1/14 (7.1%)
Gastroesophageal reflux disease	1/40 (2.5%)		1/14 (7.1%)
Nausea	16/40 (40%)		8/14 (57.1%)
Oral pain	3/40 (7.5%)		0/14 (0%)
Rectal hemorrhage	0/40 (0%)		1/14 (7.1%)
Stomach pain	0/40 (0%)		1/14 (7.1%)
Vomiting	6/40 (15%)		4/14 (28.6%)
General disorders
Chills	3/40 (7.5%)		1/14 (7.1%)
Edema face	5/40 (12.5%)		0/14 (0%)
Edema limbs	4/40 (10%)		1/14 (7.1%)
Facial pain	2/40 (5%)		0/14 (0%)
Fatigue	24/40 (60%)		9/14 (64.3%)
Fever	2/40 (5%)		0/14 (0%)
Flu like symptoms	0/40 (0%)		1/14 (7.1%)
Non-cardiac chest pain	5/40 (12.5%)		1/14 (7.1%)
Pain	8/40 (20%)		2/14 (14.3%)
Immune system disorders
Allergic reaction	2/40 (5%)		0/14 (0%)
Infections and infestations
Infections and infestations	1/40 (2.5%)		1/14 (7.1%)
Lung infection	0/40 (0%)		1/14 (7.1%)
Investigations
Activated partial thromboplastin time prolonged	0/40 (0%)		1/14 (7.1%)
Alanine aminotransferase increased	10/40 (25%)		4/14 (28.6%)
Alkaline phosphatase increased	7/40 (17.5%)		0/14 (0%)
Aspartate aminotransferase increased	9/40 (22.5%)		5/14 (35.7%)
CD4 lymphocytes decreased	1/40 (2.5%)		1/14 (7.1%)
Creatinine increased	2/40 (5%)		1/14 (7.1%)
INR increased	0/40 (0%)		1/14 (7.1%)
Lymphocyte count decreased	6/40 (15%)		3/14 (21.4%)
Neutrophil count decreased	4/40 (10%)		0/14 (0%)
Platelet count decreased	7/40 (17.5%)		0/14 (0%)
Weight loss	2/40 (5%)		3/14 (21.4%)
White blood cell decreased	4/40 (10%)		0/14 (0%)
Metabolism and nutrition disorders
Anorexia	10/40 (25%)		3/14 (21.4%)
Dehydration	0/40 (0%)		1/14 (7.1%)
Hyperglycemia	11/40 (27.5%)		2/14 (14.3%)
Hyperkalemia	6/40 (15%)		1/14 (7.1%)
Hypoalbuminemia	3/40 (7.5%)		0/14 (0%)
Hypocalcemia	2/40 (5%)		3/14 (21.4%)
Hyponatremia	4/40 (10%)		2/14 (14.3%)
Hypophosphatemia	2/40 (5%)		2/14 (14.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/40 (10%)		3/14 (21.4%)
Back pain	7/40 (17.5%)		2/14 (14.3%)
Chest wall pain	3/40 (7.5%)		2/14 (14.3%)
Generalized muscle weakness	2/40 (5%)		0/14 (0%)
Myalgia	4/40 (10%)		1/14 (7.1%)
Pain in extremity	2/40 (5%)		0/14 (0%)
Nervous system disorders
Dizziness	1/40 (2.5%)		4/14 (28.6%)
Dysgeusia	5/40 (12.5%)		2/14 (14.3%)
Headache	16/40 (40%)		4/14 (28.6%)
Peripheral motor neuropathy	1/40 (2.5%)		1/14 (7.1%)
Peripheral sensory neuropathy	4/40 (10%)		0/14 (0%)
Somnolence	0/40 (0%)		1/14 (7.1%)
Psychiatric disorders
Anxiety	2/40 (5%)		1/14 (7.1%)
Depression	2/40 (5%)		2/14 (14.3%)
Insomnia	3/40 (7.5%)		1/14 (7.1%)
Libido decreased	0/40 (0%)		1/14 (7.1%)
Renal and urinary disorders
Urinary tract pain	0/40 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/40 (0%)		1/14 (7.1%)
Aspiration	1/40 (2.5%)		1/14 (7.1%)
Bronchopulmonary hemorrhage	0/40 (0%)		1/14 (7.1%)
Cough	4/40 (10%)		5/14 (35.7%)
Dyspnea	12/40 (30%)		6/14 (42.9%)
Epistaxis	1/40 (2.5%)		3/14 (21.4%)
Hoarseness	1/40 (2.5%)		1/14 (7.1%)
Pleural effusion	4/40 (10%)		0/14 (0%)
Wheezing	0/40 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Alopecia	3/40 (7.5%)		1/14 (7.1%)
Dry skin	3/40 (7.5%)		1/14 (7.1%)
Nipple sensitivity	0/40 (0%)		1/14 (7.1%)
Palmar-plantar erythrodysesthesia syndrome	0/40 (0%)		1/14 (7.1%)
Pruritus	2/40 (5%)		0/14 (0%)
Rash acneiform	3/40 (7.5%)		1/14 (7.1%)
Rash maculo-papular	12/40 (30%)		2/14 (14.3%)
Skin erosion	0/40 (0%)		1/14 (7.1%)
Vascular disorders
Hot flashes	1/40 (2.5%)		1/14 (7.1%)
Hypertension	3/40 (7.5%)		1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.