S0722: Everolimus in Treating Patients With Pleural Malignant Mesothelioma That Cannot Be Removed By Surgery

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00770120
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 61
• Locations: 129
• Arm: 1
• Duration (Months): 64
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Everolimus 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 everolimus works in treating patients with pleural malignant mesothelioma that cannot be removed by surgery.

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

Detailed Description

OBJECTIVES:

Primary

• To determine the 4-month progression-free survival in patients with unresectable malignant pleural mesothelioma treated with everolimus.

Secondary

• To determine the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in patients with measurable disease by RECIST and modified RECIST criteria.

• To determine overall survival of these patients.

• To evaluate the frequency and severity of toxicities associated with this treatment regimen.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of mTOR Inhibitor, Everolimus (RAD001), in Malignant Pleural Mesothelioma (MPM)
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Everolimus Daily oral Everolimus 10 mg/day	Drug: everolimus

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival [Every 8 weeks until disease progression, up to 3 years.]

   Progression-Free Survival was defined as the duration from the date of registration until the date of disease progression per RECIST or death due to any cause. Patients known to be alive without evidence of disease progression were censored at the date of last contact. Disease progression was defined as a >= 20% increase over nadir in the sum of longest diameters of target lesions, unequivocal progression of non-target lesions in the opinion of the treating investigator, appearance of new lesions, symptomatic deterioration, or death due to disease

Secondary Outcome Measures

1. Response [Every 8 weeks until disease progression, up to 3 years.]

   A response was defined as either a confirmed or unconfirmed complete or partial responses as defined by RECIST. A complete response (CR) was defined as the disappearance of all disease. A partial response (PR) was defined as a >= 30% decrease in the sum of longest diameters of target lesions. A CR or PR was considered confirmed if two consecutive determinations were made at least 4 weeks apart.

2. Overall Survival [Every 8 weeks until disease progression, up to 3 years.]

   Overall survival was defined as the duration between the date of enrollment and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.

3. Frequency and Severity of Toxicities [Weekly during the first 8 weeks of treatment, then every 4 weeks while on treatment, then every 8 weeks until disease progression, then every 6 months thereafter.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant pleural mesothelioma

• Unresectable disease

• Must have measurable or nonmeasurable disease by RECIST or modified RECIST criteria

• Must have received prior systemically administered* platinum-based chemotherapy and meets the following criteria:

• No more than 2 prior systemic therapeutic regimens allowed (including biologics, targeted, and immunotherapies)

• At least 1 regimen must have been platinum-based

• Neoadjuvant and/or adjuvant systemic therapy is not counted as a prior regimen, assuming ≥ 12 weeks have elapsed between the end of neoadjuvant/adjuvant therapy and development of progressive disease NOTE: *Pleural space washing with cisplatin does not constitute systemic administration

• No known CNS metastases

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Serum bilirubin normal

• AST or ALT ≤ 1.5 times upper limit of normal (ULN)

• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No evidence of bleeding diathesis or coagulopathy

• Previous pulmonary embolism allowed provided the patient is on therapeutic low molecular weight heparin injections or warfarin AND no evidence of bleeding

• Patients on therapeutic warfarin must have an INR of < 5 within 28 days prior to registration

• No pathologic condition other than mesothelioma that carries a high risk of bleeding

• No known HIV positivity

• No gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for IV alimentation, or active peptic ulcer disease

• No other prior malignancy allowed except for any of the following:

• Adequately treated basal cell or squamous cell skin cancer

• In situ cervical cancer

• Adequately treated stage I or II cancer from which the patient is currently in complete remission

• Any other cancer from which patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy

• At least 28 days since prior systemic therapy (42 days for nitrosoureas or mitomycin

• At least 28 days since prior thoracic or other major surgery (e.g., pleurectomy or pleurodesis) and no anticipated need for major surgical procedures during study

• At least 14 days since prior radiotherapy

• No prior surgical procedure affecting absorption

• No prior chronic, systemic corticosteroids or other immunosuppressive agent, except corticosteroids equivalent to prednisone ≤ 20 mg daily

• Must have been on a stable dosage regimen for ≥ 4 weeks

• Topical and inhaled corticosteroids allowed

• No prior mTOR inhibitor therapy (i.e., rapamycin, everolimus, or temsirolimus)

• No concurrent immunization with attenuated live vaccines

• No concurrent antiretroviral therapy for HIV-positive patients

• No other concurrent investigational therapy

• No other concurrent anticancer agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
3	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California	United States	95901
4	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California	United States	92868
5	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California	United States	94588
6	University of California Davis Cancer Center	Sacramento	California	United States	95817
7	San Luis Valley Regional Medical Center	Alamosa	Colorado	United States	81101
8	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado	United States	80045
9	Shaw Regional Cancer Center	Edwards	Colorado	United States	81632
10	Valley View Hospital Cancer Center	Glenwood Springs	Colorado	United States	81601
11	Montrose Memorial Hospital Cancer Center	Montrose	Colorado	United States	81401
12	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
13	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
14	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
15	Edward Hospital Cancer Center	Naperville	Illinois	United States	60540
16	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
17	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
18	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
19	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
20	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
21	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
22	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
23	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
24	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
25	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
26	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67905
27	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
28	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
29	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
30	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
31	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
32	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
33	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
34	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
35	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
36	CCOP - Wichita	Wichita	Kansas	United States	67214
37	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
38	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
39	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
40	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
41	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
42	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
43	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
44	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
45	Hurley Medical Center	Flint	Michigan	United States	48503
46	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
47	Foote Memorial Hospital	Jackson	Michigan	United States	49201
48	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
49	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
50	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
51	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
52	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
53	St. John Macomb Hospital	Warren	Michigan	United States	48093
54	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
55	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
56	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
57	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
58	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
59	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
60	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
61	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
62	Northern Montana Hospital	Havre	Montana	United States	59501
63	St. Peter's Hospital	Helena	Montana	United States	59601
64	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
65	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
66	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
67	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
68	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
69	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
70	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
71	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
72	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
73	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
74	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
75	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
76	CCOP - Columbus	Columbus	Ohio	United States	43215
77	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
78	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
79	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
80	Grandview Hospital	Dayton	Ohio	United States	45405
81	Good Samaritan Hospital	Dayton	Ohio	United States	45406
82	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
83	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
84	CCOP - Dayton	Dayton	Ohio	United States	45420
85	Grady Memorial Hospital	Delaware	Ohio	United States	43015
86	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
87	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
88	Wayne Hospital	Greenville	Ohio	United States	45331
89	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
90	Fairfield Medical Center	Lancaster	Ohio	United States	43130
91	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
92	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
93	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
94	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
95	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
96	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
97	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
98	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
99	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
100	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
101	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
102	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
103	Willamette Falls Hospital	Oregon City	Oregon	United States	97045
104	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
105	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
106	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
107	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
108	U.T. Medical Center Cancer Institute	Knoxville	Tennessee	United States	37920-6999
109	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
110	Danville Regional Medical Center	Danville	Virginia	United States	24541
111	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia	United States	24273
112	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
113	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
114	Columbia Basin Hematology	Kennewick	Washington	United States	99336
115	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98273
116	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington	United States	98370
117	Harborview Medical Center	Seattle	Washington	United States	98104
118	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
119	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
120	Group Health Central Hospital	Seattle	Washington	United States	98112
121	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
122	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
123	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
124	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
125	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
126	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington	United States	98684
127	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
128	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
129	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Sai-Hong I. Ou, MD, PhD, Chao Family Comprehensive Cancer Center
• Study Chair: Linda Garland, MD, University of Arizona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00770120
• Other Study ID Numbers: CDR0000616162; S0722; U10CA032102
• First Posted: Oct 9, 2008
• Last Update Posted: Mar 6, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Southwest Oncology Group: recurrent malignant mesothelioma; stage II malignant mesothelioma; stage III malignant mesothelioma; stage IV malignant mesothelioma
• Additional relevant MeSH terms: Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms; Everolimus

Study Results

Participant Flow

Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day everolimus
Period Title: Overall Study
STARTED	61
Eligible	60
Not Analyzable	1
COMPLETED	0
NOT COMPLETED	61

Baseline Characteristics

Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day everolimus
Overall Participants	59
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	14 23.7%
Male	45 76.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 15.3%
Not Hispanic or Latino	47 79.7%
Unknown or Not Reported	3 5.1%
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 1.7%
White	55 93.2%
More than one race	0 0%
Unknown or Not Reported	3 5.1%
Histology (participants) [Number]
Epithelial	36 61%
Mesothelioma, NOS	17 28.8%
Biphasic	4 6.8%
Not Reported	2 3.4%
Number of Metastatic Sites (participants) [Number]
None	5 8.5%
Single	23 39%
Multiple	31 52.5%
Prior Systemic Regimens (participants) [Number]
1 Regimen	34 57.6%
2 Regimens	25 42.4%
Performance Status (participants) [Number]
0	13 22%
1	46 78%
Weight Loss Last 6 Months (participants) [Number]
< 5%	47 79.7%
5% - < 10%	6 10.2%
10% - 20%	6 10.2%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival
Description	Progression-Free Survival was defined as the duration from the date of registration until the date of disease progression per RECIST or death due to any cause. Patients known to be alive without evidence of disease progression were censored at the date of last contact. Disease progression was defined as a >= 20% increase over nadir in the sum of longest diameters of target lesions, unequivocal progression of non-target lesions in the opinion of the treating investigator, appearance of new lesions, symptomatic deterioration, or death due to disease
Time Frame	Every 8 weeks until disease progression, up to 3 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day everolimus
Measure Participants	59
Median (95% Confidence Interval) [months]	3.0

2. Secondary Outcome

Title	Response
Description	A response was defined as either a confirmed or unconfirmed complete or partial responses as defined by RECIST. A complete response (CR) was defined as the disappearance of all disease. A partial response (PR) was defined as a >= 30% decrease in the sum of longest diameters of target lesions. A CR or PR was considered confirmed if two consecutive determinations were made at least 4 weeks apart.
Time Frame	Every 8 weeks until disease progression, up to 3 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day everolimus
Measure Participants	45
Number (95% Confidence Interval) [percentage of overall response rate]	2

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the duration between the date of enrollment and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.
Time Frame	Every 8 weeks until disease progression, up to 3 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day everolimus
Measure Participants	59
Median (95% Confidence Interval) [months]	6.3

4. Secondary Outcome

Title	Frequency and Severity of Toxicities
Time Frame	Weekly during the first 8 weeks of treatment, then every 4 weeks while on treatment, then every 8 weeks until disease progression, then every 6 months thereafter.

Outcome Measure Data

Analysis Population Description

Number of Subjects With Greater Than Grade 2 Toxicity

Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day
Measure Participants	59
Anorexia	1 1.7%
Confusion	1 1.7%
Dehydration	2 3.4%
Diarrhea	1 1.7%
Dyspnea (shortness of breath)	3 5.1%
Fatigue (asthenia, lethargy, malaise)	6 10.2%
Glucose, serum-high (hyperglycemia)	3 5.1%
Hemoglobin	4 6.8%
INR (of prothrombin time)	1 1.7%
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	1 1.7%
Infection with unknown ANC - Lung (pneumonia)	3 5.1%
Left ventricular systolic dysfunction	1 1.7%
Lymphopenia	2 3.4%
Mucositis/stomatitis (clinical exam) - Oral cavity	1 1.7%
Mucositis/stomatitis (functional/symp) - Oral cav	1 1.7%
Muscle weakness, not d/t neuropathy - body/general	2 3.4%
Pneumonitis/pulmonary infiltrates	2 3.4%
Rash/desquamation	1 1.7%
Triglyceride, serum-high (hypertriglyceridemia)	2 3.4%

Adverse Events

Time Frame	From date of registration to 3 years post registration or death (whichever occurs first).
Adverse Event Reporting Description	All SAEs and AEs.
Arm/Group Title	Everolimus
Arm/Group Description	Daily oral Everolimus 10 mg/day
All Cause Mortality
	Everolimus
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Everolimus
	Affected / at Risk (%)	# Events
Total	25/59 (42.4%)
Blood and lymphatic system disorders
Hemoglobin	3/59 (5.1%)
Cardiac disorders
Left ventricular systolic dysfunction	1/59 (1.7%)
Pericardial effusion (non-malignant)	1/59 (1.7%)
Gastrointestinal disorders
Diarrhea	2/59 (3.4%)
Hemorrhage, GI - Oral cavity	1/59 (1.7%)
General disorders
Death not associated with CTCAE term - Death NOS	5/59 (8.5%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	1/59 (1.7%)
Infection with unknown ANC - Lung (pneumonia)	4/59 (6.8%)
Investigations
Neutrophils/granulocytes (ANC/AGC)	1/59 (1.7%)
Metabolism and nutrition disorders
Dehydration	1/59 (1.7%)
Musculoskeletal and connective tissue disorders
Pain - Back	1/59 (1.7%)
Pain - Chest wall	1/59 (1.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	3/59 (5.1%)
Psychiatric disorders
Confusion	1/59 (1.7%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/59 (1.7%)
Atelectasis	1/59 (1.7%)
Dyspnea (shortness of breath)	8/59 (13.6%)
Hypoxia	1/59 (1.7%)
Pleural effusion (non-malignant)	2/59 (3.4%)
Pneumonitis/pulmonary infiltrates	4/59 (6.8%)
Vascular disorders
Thrombosis/thrombus/embolism	4/59 (6.8%)
Other (Not Including Serious) Adverse Events
	Everolimus
	Affected / at Risk (%)	# Events
Total	58/59 (98.3%)
Blood and lymphatic system disorders
Hemoglobin	38/59 (64.4%)
Cardiac disorders
SVT and nodal arrhythmia - Sinus tachycardia	4/59 (6.8%)
Gastrointestinal disorders
Constipation	13/59 (22%)
Diarrhea	14/59 (23.7%)
Dry mouth/salivary gland (xerostomia)	3/59 (5.1%)
Dysphagia (difficulty swallowing)	3/59 (5.1%)
Flatulence	3/59 (5.1%)
Gastrointestinal-Other	5/59 (8.5%)
Hemorrhoids	3/59 (5.1%)
Mucositis/stomatitis (clinical exam) - Oral cavity	19/59 (32.2%)
Mucositis/stomatitis (functional/symp) - Oral cav	10/59 (16.9%)
Nausea	21/59 (35.6%)
Pain - Abdomen NOS	9/59 (15.3%)
Pain - Oral cavity	3/59 (5.1%)
Vomiting	10/59 (16.9%)
General disorders
Constitutional Symptoms-Other	3/59 (5.1%)
Edema: limb	8/59 (13.6%)
Edema: trunk/genital	3/59 (5.1%)
Fatigue (asthenia, lethargy, malaise)	41/59 (69.5%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	4/59 (6.8%)
Pain - Chest/thorax NOS	8/59 (13.6%)
Pain-Other	4/59 (6.8%)
Rigors/chills	4/59 (6.8%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	5/59 (8.5%)
AST, SGOT	8/59 (13.6%)
Alkaline phosphatase	6/59 (10.2%)
Cholesterol, serum-high (hypercholesterolemia)	19/59 (32.2%)
Creatinine	14/59 (23.7%)
Leukocytes (total WBC)	12/59 (20.3%)
Lymphopenia	9/59 (15.3%)
Metabolic/Laboratory-Other	3/59 (5.1%)
Neutrophils/granulocytes (ANC/AGC)	4/59 (6.8%)
Platelets	16/59 (27.1%)
Weight loss	16/59 (27.1%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	15/59 (25.4%)
Anorexia	27/59 (45.8%)
Calcium, serum-low (hypocalcemia)	8/59 (13.6%)
Dehydration	6/59 (10.2%)
Glucose, serum-high (hyperglycemia)	26/59 (44.1%)
Potassium, serum-high (hyperkalemia)	5/59 (8.5%)
Potassium, serum-low (hypokalemia)	5/59 (8.5%)
Sodium, serum-low (hyponatremia)	8/59 (13.6%)
Triglyceride, serum-high (hypertriglyceridemia)	30/59 (50.8%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	7/59 (11.9%)
Pain - Back	5/59 (8.5%)
Pain - Chest wall	10/59 (16.9%)
Nervous system disorders
Dizziness	6/59 (10.2%)
Neuropathy: sensory	10/59 (16.9%)
Pain - Head/headache	4/59 (6.8%)
Taste alteration (dysgeusia)	8/59 (13.6%)
Psychiatric disorders
Insomnia	6/59 (10.2%)
Mood alteration - anxiety	7/59 (11.9%)
Renal and urinary disorders
Urinary frequency/urgency	3/59 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	23/59 (39%)
Dyspnea (shortness of breath)	30/59 (50.8%)
Hemorrhage, pulmonary/upper respiratory - Nose	5/59 (8.5%)
Hypoxia	3/59 (5.1%)
Pulmonary/Upper Respiratory-Other	3/59 (5.1%)
Voice changes/dysarthria	4/59 (6.8%)
Skin and subcutaneous tissue disorders
Pruritus/itching	5/59 (8.5%)
Rash/desquamation	11/59 (18.6%)
Rash: acne/acneiform	5/59 (8.5%)
Sweating (diaphoresis)	4/59 (6.8%)
Vascular disorders
Hypertension	5/59 (8.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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