Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00509041
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 37
• Arm: 1
• Duration (Months): 64
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with previously treated malignant mesothelioma.

Condition or Disease	Intervention/Treatment	Phase
Malignant Mesothelioma	Drug: dasatinib	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the rate of progression-free survival (PFS) at 24 weeks (or 5.5 months) in patients with malignant mesothelioma treated with dasatinib.

Secondary

• To determine the response rate (partial response [PR] and complete response [CR]) in patients with malignant mesothelioma treated with dasatinib.

• To determine the response duration in patients with malignant mesothelioma treated with dasatinib.

• To describe the overall survival (OS) of patients with malignant mesothelioma treated with dasatinib.

• To describe the toxicity profile of dasatinib in patients with malignant mesothelioma.

• To determine whether the amount of expression of EphA2 and PDGFRβ, as measured by immunohistochemistry from tumor specimens, correlates with PFS in patients with malignant mesothelioma.

• To determine whether plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related protein correlate with PFS in patients with malignant mesothelioma.

• To determine whether inhibition of Src phosphorylation in PBMC correlates with PFS.

• To assess inhibition of phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue by dasatinib.

OUTLINE: Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative studies. Tumor tissue samples are analyzed for EphA2 and PDGFRβ expression by immunohistochemistry. Tumor tissue samples may also be analyzed for phosphorylation of Src, EphA2, and PDGFRβ by western blot. Blood samples are analyzed for concentration of VEGF and PDGF by quantitative sandwich enzyme immunoassay technique; mesothelin-related protein level by Mesomark® assay; CSF-1 level by ELISA assay; and phosphorylation of Src by phospho-Src (pTyr418) human ELISA.

After completion of study treatment, patients are followed at least every 2 months for 1 year, then every 4 months for 1 year, then every 6 months for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib Use of dasatinib in treatment of pts with previously treated malignant mesothelioma	Drug: dasatinib; 50 mg PO bid

Outcome Measures

Primary Outcome Measures

1. 24 Week Progression Free Survival [24 weeks]

   Percentage of participants who were alive and progression free at 24 weeks. The 24 week progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

Secondary Outcome Measures

1. Number of Participants With Overall Tumor Response [Duration of study until progression (up to 3 years)]

   Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs.

2. Overall Survival [Time from registration to death (up to 3 years)]

   Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

3. Progression Free Survival [Time from registration to progression or death (up to 3 years)]

   Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant mesothelioma of any of the following subtypes:

• Epithelial

• Sarcomatoid

• Mixed

• Any site of origin of malignant mesothelioma allowed including, but not limited to, any of the following:

• Pleura

• Peritoneum

• Pericardium

• Tunica vaginalis

• Pathology blocks or slides from a core surgical biopsy must be available

• Not amenable to curative surgery

• Measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (CT scan , MRI, or x-ray) or as ≥ 10 mm with spiral CT scan

• Patients with pleural rind only disease must have at least one level with one rind measurement ≥ 1.5 cm

• Lesions that are considered nonmeasurable include the following:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Prior treatment with one and only one systemic chemotherapy regimen, which must have included pemetrexed disodium required

• Treatment may have been with pemetrexed disodium alone or in combination with any other agent

• No symptomatic pleural effusions, unless the patient undergoes a therapeutic thoracentesis

• Patients with pleural effusions who have had a pleurodesis are eligible

• No known brain metastases

• May be registered on CALGB-150707 companion study

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Granulocytes ≥ 1,500/μL

• Platelet count ≥ 100,000/μL

• Total bilirubin ≤ 2 x upper limit of normal (ULN)

• AST (SGOT) ≤ 2.5 x ULN

• Creatinine clearance ≥ 60 mL/min

• INR < 1.5

• PTT < 40 seconds

• QTc < 450 msec

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No significant cardiac disease, including any of the following:

• New York Heart Association (NYHA) class III-IV congestive heart failure (CHF)

• Unstable angina

• Myocardial infarction or ventricular tachyarrhythmia within 6 months of study entry

• Ejection fraction less than institutional normal (in patients with a history of CHF or currently with NYHA class I or II CHF)

• Prolonged QTc > 450 msec (Fridericia correction)

• Major conduction abnormality, unless a cardiac pacemaker is present

• Hypokalemia or hypomagnesemia that cannot be corrected

• No history of significant bleeding disorder unrelated to cancer, including any of the following:

• Congenital bleeding disorder (e.g., von Willebrand disease)

• Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII antibodies)

• Ongoing or recent (≤ 3 months) significant GI bleeding or hemoptysis

• No requirement for supplemental oxygen (i.e., pulse oximetry < 89% at rest)

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior pemetrexed disodium-containing chemotherapy

• At least 4 weeks since prior major surgery

• At least 4 weeks since prior radiation therapy

• Measurable disease must be outside the radiation port

• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed

• Intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy

• At least 7 days since prior and no concurrent antithrombotic or anti-platelet agents, including any of the following:

• Aspirin or aspirin-containing combinations

• Clopidogrel

• Dipyridamole

• Tirofiban

• Epoprostenol

• Eptifibatide

• Cilostazol

• Abciximab

• Ticlopidine

• Warfarin

• Low-dose warfarin for prophylaxis to prevent catheter thrombosis allowed

• Heparin or low molecular weight heparin

• Heparin for IV line flush allowed

• At least 7 days since prior and no concurrent use of the following drugs:

• Itraconazole

• Ketoconazole (at doses > 200 mg/day)

• Miconazole

• Voriconazole

• Telithromycin

• Primidone

• Rifabutin

• Rifampin

• St. John's wort

• Carbamazepine

• Oxcarbazepine

• Rifapentine

• Phenobarbital

• Phenytoin

• Quinidine

• Procainamide

• Disopyramide

• Amiodarone

• Sotalol

• Ibutilide

• Dofetilide

• Erythromycin

• Clarithromycin

• Chlorpromazine

• Haloperidol

• Mesoridazine

• Thioridazine

• Pimozide

• Bepridil

• Droperidol

• Halofantrine

• Levomethadyl

• Sparfloxacin

• No concurrent H2 blockers or proton pump inhibitors

• No bisphosphonate therapy during the first 8 weeks of study treatment

• No concurrent hormones or other chemotherapeutic agents except for steroids administered for dasatinib-related pleural effusion or hormones administered for non-disease-related conditions (e.g., insulin for diabetes)

• No concurrent palliative radiation therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
2	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
3	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
4	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
5	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
6	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
7	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
8	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
9	Elkhart General Hospital	Elkhart	Indiana	United States	46515
10	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46845
11	Howard Community Hospital	Kokomo	Indiana	United States	46904
12	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
13	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
14	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
15	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
16	South Bend Clinic	South Bend	Indiana	United States	46617
17	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
18	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
19	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
20	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
21	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
22	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota	United States	55455
23	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
24	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
25	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
26	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
27	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
28	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
29	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
30	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
31	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
32	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
33	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
34	CCOP - Greenville	Greenville	South Carolina	United States	29615
35	Mountainview Medical	Berlin	Vermont	United States	05602
36	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
37	Danville Regional Medical Center	Danville	Virginia	United States	24541

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Arkadiusz Dudek, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00509041
• Other Study ID Numbers: CALGB-30601; U10CA031946; CALGB-30601; CDR0000558362
• First Posted: Jul 31, 2007
• Last Update Posted: Aug 11, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: advanced malignant mesothelioma; epithelial mesothelioma; recurrent malignant mesothelioma; sarcomatous mesothelioma
• Additional relevant MeSH terms: Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms; Dasatinib

Study Results

Participant Flow

Recruitment Details	Between September 2007 to August 2009, 46 participants were recruited.
Pre-assignment Detail	Three (3) participants withdrew from the study before treatment initiation; therefore 43 participants were eligible for evaluation

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
Period Title: Overall Study
STARTED	43
COMPLETED	43
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
Overall Participants	43
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	12 27.9%
Male	31 72.1%
Region of Enrollment (participants) [Number]
United States	43 100%
ECOG Performance Score (participants) [Number]
0 - Fully Active	19 44.2%
1 - Ambulatory, restricted strenuous activity	24 55.8%
Site of origin (participants) [Number]
Pleura	36 83.7%
Peritoneum	6 14%
Other	1 2.3%
Histology (participants) [Number]
Epithelial	33 76.7%
Biphasic	5 11.6%
Sarcomatoid	2 4.7%
Not reported	3 7%
Prior chemotherapy (participants) [Number]
Yes	43 100%
No	0 0%
Prior radiation (participants) [Number]
Yes	6 14%
No	37 86%
Prior surgery (participants) [Number]
Yes	23 53.5%
No	20 46.5%

Outcome Measures

1. Primary Outcome

Title	24 Week Progression Free Survival
Description	Percentage of participants who were alive and progression free at 24 weeks. The 24 week progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
Measure Participants	43
Number (95% Confidence Interval) [percentage of participants]	23 53.5%

2. Secondary Outcome

Title	Number of Participants With Overall Tumor Response
Description	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs.
Time Frame	Duration of study until progression (up to 3 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
Measure Participants	43
Complete Response	0 0%
Partial Response	2 4.7%

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Time Frame	Time from registration to death (up to 3 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
Measure Participants	43
Median (95% Confidence Interval) [weeks]	26.1

4. Secondary Outcome

Title	Progression Free Survival
Description	Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time Frame	Time from registration to progression or death (up to 3 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
Measure Participants	43
Median (95% Confidence Interval) [weeks]	9.1

Adverse Events

Arm/Group Title	Dasatinib
Arm/Group Description	Use of dasatinib (50 mg orally twice a day) in treatment of pts with previously treated malignant mesothelioma
All Cause Mortality
	Dasatinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	15/43 (34.9%)
Blood and lymphatic system disorders
Hemoglobin decreased	8/43 (18.6%)	11
Cardiac disorders
Pericardial effusion	2/43 (4.7%)	2
Eye disorders
Watering eyes	1/43 (2.3%)	1
Gastrointestinal disorders
Abdominal distension	2/43 (4.7%)	2
Abdominal pain	2/43 (4.7%)	2
Constipation	5/43 (11.6%)	5
Diarrhea	7/43 (16.3%)	7
Dry mouth	1/43 (2.3%)	1
Dyspepsia	1/43 (2.3%)	1
Flatulence	1/43 (2.3%)	1
Hemorrhoids	1/43 (2.3%)	1
Nausea	7/43 (16.3%)	8
Peritoneal pain	1/43 (2.3%)	1
Small intestinal obstruction	1/43 (2.3%)	1
Vomiting	4/43 (9.3%)	4
General disorders
Chest pain	3/43 (7%)	3
Chills	1/43 (2.3%)	1
Disease progression	1/43 (2.3%)	1
Edema limbs	3/43 (7%)	3
Fatigue	10/43 (23.3%)	13
Fever	1/43 (2.3%)	1
Injection site reaction	1/43 (2.3%)	1
Localized edema	1/43 (2.3%)	1
Sudden death	1/43 (2.3%)	1
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/43 (2.3%)	1
Pleural infection	1/43 (2.3%)	1
Pneumonia	3/43 (7%)	3
Sinusitis	1/43 (2.3%)	1
Investigations
Alanine aminotransferase increased	2/43 (4.7%)	2
Alkaline phosphatase increased	2/43 (4.7%)	2
Aspartate aminotransferase increased	3/43 (7%)	3
Creatinine increased	3/43 (7%)	3
INR increased	1/43 (2.3%)	1
Leukocyte count decreased	1/43 (2.3%)	1
Lymphocyte count decreased	3/43 (7%)	4
Weight loss	4/43 (9.3%)	4
Metabolism and nutrition disorders
Anorexia	6/43 (14%)	6
Blood glucose increased	4/43 (9.3%)	4
Dehydration	2/43 (4.7%)	2
Serum albumin decreased	7/43 (16.3%)	8
Serum calcium decreased	6/43 (14%)	7
Serum glucose decreased	1/43 (2.3%)	1
Serum magnesium increased	2/43 (4.7%)	2
Serum potassium decreased	1/43 (2.3%)	1
Serum potassium increased	2/43 (4.7%)	2
Serum sodium decreased	6/43 (14%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	3/43 (7%)	3
Back pain	1/43 (2.3%)	1
Myalgia	2/43 (4.7%)	2
Pain in extremity	1/43 (2.3%)	1
Nervous system disorders
Dizziness	1/43 (2.3%)	1
Dysgeusia	2/43 (4.7%)	2
Headache	1/43 (2.3%)	1
Peripheral motor neuropathy	2/43 (4.7%)	2
Peripheral sensory neuropathy	1/43 (2.3%)	1
Psychiatric disorders
Confusion	1/43 (2.3%)	1
Insomnia	1/43 (2.3%)	1
Psychosis	2/43 (4.7%)	2
Renal and urinary disorders
Glomerular filtration rate decreased	1/43 (2.3%)	1
Urogenital disorder	1/43 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/43 (2.3%)	1
Allergic rhinitis	1/43 (2.3%)	1
Cough	3/43 (7%)	3
Dyspnea	5/43 (11.6%)	6
Hypoxia	1/43 (2.3%)	1
Pleural effusion	4/43 (9.3%)	4
Pleuritic pain	1/43 (2.3%)	1
Pneumonitis	1/43 (2.3%)	1
Respiratory disorder	1/43 (2.3%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Dasatinib
	Affected / at Risk (%)	# Events
Total	35/43 (81.4%)
Blood and lymphatic system disorders
Hemoglobin decreased	24/43 (55.8%)	64
Cardiac disorders
Pericardial effusion	1/43 (2.3%)	1
Pericarditis	1/43 (2.3%)	1
Ventricular tachycardia	1/43 (2.3%)	1
Gastrointestinal disorders
Abdominal distension	1/43 (2.3%)	1
Abdominal pain	4/43 (9.3%)	4
Ascites	1/43 (2.3%)	1
Constipation	4/43 (9.3%)	5
Diarrhea	14/43 (32.6%)	19
Dyspepsia	3/43 (7%)	3
Gastritis	1/43 (2.3%)	1
Gastrointestinal disorder	1/43 (2.3%)	1
Hemorrhoids	1/43 (2.3%)	1
Nausea	11/43 (25.6%)	19
Stomach pain	1/43 (2.3%)	2
Vomiting	6/43 (14%)	9
General disorders
Chest pain	3/43 (7%)	5
Chills	3/43 (7%)	3
Disease progression	2/43 (4.7%)	2
Edema limbs	2/43 (4.7%)	7
Fatigue	24/43 (55.8%)	57
Fever	4/43 (9.3%)	5
Injection site reaction	1/43 (2.3%)	1
Localized edema	1/43 (2.3%)	2
Pain	1/43 (2.3%)	1
Visceral edema	1/43 (2.3%)	1
Immune system disorders
Hypersensitivity	1/43 (2.3%)	1
Infections and infestations
Gingival infection	1/43 (2.3%)	1
Pneumonia	1/43 (2.3%)	1
Rhinitis infective	1/43 (2.3%)	2
Sinusitis	1/43 (2.3%)	2
Upper aerodigestive tract infection	1/43 (2.3%)	3
Injury, poisoning and procedural complications
Arterial injury	1/43 (2.3%)	1
Investigations
Alanine aminotransferase increased	2/43 (4.7%)	5
Alkaline phosphatase increased	2/43 (4.7%)	6
Aspartate aminotransferase increased	3/43 (7%)	6
Creatinine increased	1/43 (2.3%)	1
Electrocardiogram QTc interval prolonged	1/43 (2.3%)	1
INR increased	1/43 (2.3%)	1
Leukocyte count decreased	1/43 (2.3%)	1
Lymphocyte count decreased	6/43 (14%)	9
Platelet count decreased	3/43 (7%)	3
Weight loss	7/43 (16.3%)	18
Metabolism and nutrition disorders
Anorexia	11/43 (25.6%)	13
Blood glucose increased	6/43 (14%)	10
Dehydration	1/43 (2.3%)	1
Serum albumin decreased	5/43 (11.6%)	6
Serum calcium decreased	4/43 (9.3%)	4
Serum calcium increased	1/43 (2.3%)	1
Serum glucose decreased	1/43 (2.3%)	1
Serum magnesium decreased	1/43 (2.3%)	1
Serum magnesium increased	1/43 (2.3%)	1
Serum phosphate decreased	4/43 (9.3%)	4
Serum potassium decreased	2/43 (4.7%)	4
Serum potassium increased	1/43 (2.3%)	1
Serum sodium decreased	10/43 (23.3%)	10
Serum sodium increased	1/43 (2.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/43 (4.7%)	3
Back pain	3/43 (7%)	4
Bone pain	1/43 (2.3%)	1
Chest wall pain	5/43 (11.6%)	5
Pain in extremity	1/43 (2.3%)	1
Nervous system disorders
Dizziness	3/43 (7%)	7
Dysgeusia	2/43 (4.7%)	3
Headache	8/43 (18.6%)	10
Memory impairment	1/43 (2.3%)	1
Neurological disorder NOS	1/43 (2.3%)	1
Peripheral sensory neuropathy	3/43 (7%)	3
Psychiatric disorders
Anxiety	1/43 (2.3%)	1
Confusion	1/43 (2.3%)	1
Depression	1/43 (2.3%)	1
Insomnia	3/43 (7%)	3
Renal and urinary disorders
Urogenital disorder	1/43 (2.3%)	6
Reproductive system and breast disorders
Breast pain	1/43 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/43 (4.7%)	4
Cough	6/43 (14%)	16
Dyspnea	19/43 (44.2%)	40
Epistaxis	1/43 (2.3%)	1
Hypoxia	2/43 (4.7%)	3
Pleural effusion	8/43 (18.6%)	18
Pneumonitis	1/43 (2.3%)	2
Respiratory disorder	1/43 (2.3%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/43 (2.3%)	1
Pruritus	2/43 (4.7%)	2
Rash acneiform	2/43 (4.7%)	2
Rash desquamating	4/43 (9.3%)	7
Skin disorder	2/43 (4.7%)	2
Vascular disorders
Thrombosis	2/43 (4.7%)	2

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.