Bevacizumab and Temozolomide or Bevacizumab and Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed by Surgery

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00626405
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 95
• Locations: 259
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, paclitaxel albumin-stabilized nanoparticle formulation, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether bevacizumab is more effective when given together with temozolomide or paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in killing malignant melanoma cells.

PURPOSE: This randomized phase II trial is studying the side effects of giving temozolomide together with bevacizumab and to see how well it works compared with giving bevacizumab together with paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in treating patients with stage IV malignant melanoma that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: bevacizumab; Drug: carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: temozolomide	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the anti-tumor activity, in terms of the percentage of patients who are treated with these regimens and who are progression-free at 6 months.

• To assess the safety profile of each treatment regimen.

Secondary

• To estimate the response rate in patients treated with these regimens.

• To estimate the distribution of progression-free survival time and overall survival time of patients treated with these regimens.

Tertiary

• To examine the impact of therapy on angiogenesis and immune homeostasis.

OUTLINE: Patients are stratified according to ECOG performance status (0 vs 1) and location of metastatic disease (M1a [skin or subcutaneous tissue or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15. (closed to accrual 8/21/09)

• Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for VEGF plasma levels and analysis of changes in immune homeostasis.

Beginning at study entry, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15.	Biological: bevacizumab; Given IV over 30-90 minutes; Drug: temozolomide; Oral temozolomide on days 1-5
Experimental: Arm II Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.	Biological: bevacizumab; Given IV over 30-90 minutes; Drug: carboplatin; Given IV over 30 minutes; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Given IV over 30 minutes

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival at 6 Months [at 6 months]

   The primary endpoint is the 6 month post registration Progression-free survival (PFS) rate. Progression-free survival time is defined as the time from registration to documentation of disease progression using the RECIST criteria. Patients who died without documentation of disease progression will be considered to have progressed at death unless there is sufficient documented evidence to conclude no progression occurred prior to death. All patients, who meet the eligibility criteria, sign a consent form, and start treatment will be included in the evaluation of the 6 month PFS rate.

Secondary Outcome Measures

1. Tumor Response Rate, Calculated as a Percentage Along With it's 95% Confidence Interval [Up to 5 years]

   A confirmed tumor response is defined to be a Complete Response or Partial Response noted > as the objective status on 2 consecutive evaluations at least 8 > weeks apart. The proportion of tumor responses will be > estimated by the number of confirmed tumor responses divided > by the total number of evaluable patients. > Complete Response (CR): Disappearance of all target lesions > Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. > Progression (PD): At least a 20% increase in the sum of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. > Stable Disease (SD): Neither sufficient shrinkage to Qualify for PR nor sufficient increase to Qualify for PD taking as reference the smallest sum LD. responses will be calculated assuming that the number of > confirmed tumor responses follows a binomial distribution.

2. Overall Survival [Up to 5 years]

   Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Eligibility Criteria

Criteria

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

• Histologic confirmed diagnosis of malignant melanoma

• Stage IV disease

• Not amenable tosurgery

• Measurable disease with at least one lesion whose longest diameter canbe measured as ≥ 20 mm by CT or MRI scans OR ≥ 10 mm by spiral CT

• No disease that is measurable by physical examination only

• No brain metastases per MRI or CT

• No radiographically documented invasion of adjacent organs(duodenum, stomach, etc.) or tumor invading major blood vessels

• ECOG performance status 0-1

• Life expectancy ≥ 4 months

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL (transfusion allowed)

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Total bilirubin ≤ 1.5 mg/dL (unless Gilbert syndrome)

• AST ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Urine protein:creatinine ratio < 1.0 at screening ORproteinuria < 2+ by urine dipstick or protein ≤ 1 g by 24-hour urine collection

• Negative serum pregnancy test

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Active infection requiring parenteral antibiotics

• Poorly controlled high blood pressure (≥ 150 mm Hg systolic and/or100 mm Hg diastolic) despite treatment

• NYHA class II-IV congestive heart failure

• Serious cardiac arrhythmia requiring medication

• Myocardial infarction or unstable angina within the past 6 months

• Clinically significant peripheral vascular disease

• Deep venous thrombosis or pulmonary embolus within the past year

• Active bleeding or pathological conditions that carry high risk of bleeding (e.g., known esophageal varices)

• Serious, non-healing wound (including wounds healing by secondary intention), ulcer or bone fracture

• Abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within the past 6 months

• History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.)

• Clinically significant stroke or TIA within the past 6 months

• Seizures not controlled with standardmedical therapy

• Peripheral neuropathy ≥ grade 2

• History of other malignancy within the past 5 years except basal cell or squamous cell carcinoma of the skin treatable with local resection only or carcinoma in situ of the cervix

• Significant traumatic injury within the past 4 weeks

• History of hypertensive crisis or hypertensive encephalopathy

• Active or recent (≤ 30 days) history of hemoptysis (≥ ½ teaspoon of bright red blood per episode)

• Known hypersensitivity to any of the components of bevacizumab

• Known to be HIV positive

• Current or known history of hepatitis

• Prior adjuvant chemotherapy and/or immunotherapy for this cancer allowed

• No prior treatment with agents disrupting VEGF activity (i.e., bevacizumab,VEGF-trap, anti-VEGFR Mab)

• No ongoing need for full-dose oral or parenteral anticoagulation

• No ongoing anti-platelet treatment other than low-dose aspirin(i.e., aspirin 81 mg daily)

• No other investigational agents within the past 4 weeks

• No major surgical procedure or open biopsy within the past 4 weeks

• No fine needle aspirations or core biopsies within the past 7 days

• No prior chemotherapy in the metastatic setting

• No prior treatment with sunitinib malate or sorafenib

• No prior treatment with any taxane-based chemotherapy

• Patients who have had > 25% of their functional bone marrow irradiated are not eligible for this trial

• No adjuvant radiation therapy within the past 4 weeks

• More than 2 weeks since prior and no concurrent palliative radiation therapy

• No concurrent major surgical procedure

• No concurrent participation in another clinical study for procedures or agents that treat the same primary study malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Cancer Center	Anchorage	Alaska	United States	99508
2	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
3	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
4	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
5	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
6	St. Anthony Central Hospital	Denver	Colorado	United States	80204
7	Porter Adventist Hospital	Denver	Colorado	United States	80210
8	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
9	St. Joseph Hospital	Denver	Colorado	United States	80218
10	Rose Medical Center	Denver	Colorado	United States	80220
11	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
12	Swedish Medical Center	Englewood	Colorado	United States	80110
13	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
14	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
15	North Colorado Medical Center	Greeley	Colorado	United States	80631
16	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
17	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
18	McKee Medical Center	Loveland	Colorado	United States	80539
19	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
20	North Suburban Medical Center	Thornton	Colorado	United States	80229
21	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
22	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
23	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
24	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
25	Graham Hospital	Canton	Illinois	United States	61520
26	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
27	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
28	Eureka Community Hospital	Eureka	Illinois	United States	61530
29	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
30	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
31	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
32	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
33	Mason District Hospital	Havana	Illinois	United States	62644
34	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
35	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
36	McDonough District Hospital	Macomb	Illinois	United States	61455
37	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
38		Moline	Illinois	United States	61265
39	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
40	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
41	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
42	Community Cancer Center	Normal	Illinois	United States	61761
43	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
44	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
45	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
46	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
47	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
48	Proctor Hospital	Peoria	Illinois	United States	61614
49	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
50	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
51	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
52	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
53	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
54	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
55	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
56	Perry Memorial Hospital	Princeton	Illinois	United States	61356
57	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
58	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
59	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
60	Elkhart General Hospital	Elkhart	Indiana	United States	46515
61	Howard Community Hospital	Kokomo	Indiana	United States	46904
62	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
63	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
64	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
65	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
66	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
67	South Bend Clinic	South Bend	Indiana	United States	46617
68	McFarland Clinic, PC	Ames	Iowa	United States	50010
69		Bettendorf	Iowa	United States	52722
70	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
71	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
72	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
73	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
74	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
75	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
76	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
77	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
78	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
79	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
80	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
81	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
82	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
83	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
84	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
85	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
86	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
87	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
88	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
89	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
90	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
91	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
92	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
93	Southwest Medical Center	Liberal	Kansas	United States	67901
94	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
95	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
96	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
97	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
98	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
99	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
100	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
101	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
102	CCOP - Wichita	Wichita	Kansas	United States	67214
103	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
104	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
105	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
106	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
107	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
108	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
109	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
110	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
111	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
112	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
113	Hurley Medical Center	Flint	Michigan	United States	48503
114	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
115	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
116	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
117	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
118	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
119	Foote Memorial Hospital	Jackson	Michigan	United States	49201
120	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
121	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
122	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
123	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
124	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
125	Mercy General Health Partners	Muskegon	Michigan	United States	49443
126	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
127	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
128	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
129	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
130	Munson Medical Center	Traverse City	Michigan	United States	49684
131	St. John Macomb Hospital	Warren	Michigan	United States	48093
132	Metro Health Hospital	Wyoming	Michigan	United States	49519
133		Alexandria	Minnesota	United States	56308
134	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
135	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
136	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
137	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
138	CCOP - Duluth	Duluth	Minnesota	United States	55805
139	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
140	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
141	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
142	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
143	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
144	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
145	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
146	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
147	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
148	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
149	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
150	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
151	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
152	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
153	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
154	United Hospital	Saint Paul	Minnesota	United States	55102
155	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
156	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
157	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
158	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
159	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
160	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
161	St. John's Regional Health Center	Springfield	Missouri	United States	65804
162	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
163	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
164	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
165	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
166	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
167	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
168	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
169	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
170	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
171		Great Falls	Montana	United States	59405
172	Northern Montana Hospital	Havre	Montana	United States	59501
173	St. Peter's Hospital	Helena	Montana	United States	59601
174	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
175	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
176	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
177	Community Medical Center	Missoula	Montana	United States	59801
178	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
179	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
180	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
181	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
182	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
183	Immanuel Medical Center	Omaha	Nebraska	United States	68122
184	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
185	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
186	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
187	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
188	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
189	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
190	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
191	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
192	MeritCare Broadway	Fargo	North Dakota	United States	58122
193	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
194	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
195	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
196	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
197	North Coast Cancer Care - Clyde	Clyde	Ohio	United States	43410
198	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
199	CCOP - Columbus	Columbus	Ohio	United States	43215
200	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
201	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
202	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
203	Grandview Hospital	Dayton	Ohio	United States	45405
204	Good Samaritan Hospital	Dayton	Ohio	United States	45406
205	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
206	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
207	CCOP - Dayton	Dayton	Ohio	United States	45420
208	Grady Memorial Hospital	Delaware	Ohio	United States	43015
209	Hematology Oncology Center	Elyria	Ohio	United States	44035
210	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
211	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
212	Wayne Hospital	Greenville	Ohio	United States	45331
213	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
214	Fairfield Medical Center	Lancaster	Ohio	United States	43130
215	Lima Memorial Hospital	Lima	Ohio	United States	45804
216	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
217	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
218	St. Luke's Hospital	Maumee	Ohio	United States	43537
219	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
220	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
221	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
222	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
223	Mercy Medical Center	Springfield	Ohio	United States	45504
224	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
225	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
226	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
227	Toledo Hospital	Toledo	Ohio	United States	43606
228	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
229	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
230	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
231	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
232	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
233	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
234	Fulton County Health Center	Wauseon	Ohio	United States	43567
235	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
236	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
237	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
238	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
239	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
240	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
241	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
242	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
243	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
244	AnMed Cancer Center	Anderson	South Carolina	United States	29621
245	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
246	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
247	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
248	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
249	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
250	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
251	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
252	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
253	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
254	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
255	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
256	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
257	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
258	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
259	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

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

Investigators

• Study Chair: Svetomir Markovic, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00626405
• Other Study ID Numbers: NCCTG-N0775; NCI-2009-00667; CDR0000587708
• First Posted: Feb 29, 2008
• Last Update Posted: May 1, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Alliance for Clinical Trials in Oncology: stage IV melanoma
• Additional relevant MeSH terms: Melanoma; Paclitaxel; Bevacizumab; Carboplatin; Temozolomide; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15.> > bevacizumab: Given IV over 30-90 minutes> > temozolomide: Oral temozolomide on days 1-5	Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.> > bevacizumab: Given IV over 30-90 minutes> > carboplatin: Given IV over 30 minutes> > paclitaxel albumin-stabilized nanoparticle formulation: Given IV over 30 minutes
Period Title: Overall Study
STARTED	43	52
COMPLETED	42	51
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Arm I	Arm II	Total
Arm/Group Description	Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15.> > bevacizumab: Given IV over 30-90 minutes> > temozolomide: Oral temozolomide on days 1-5	Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.> > bevacizumab: Given IV over 30-90 minutes> > carboplatin: Given IV over 30 minutes> > paclitaxel albumin-stabilized nanoparticle formulation: Given IV over 30 minutes	Total of all reporting groups
Overall Participants	42	51	93
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	57	57	57
Sex: Female, Male (Count of Participants)
Female	18 42.9%	22 43.1%	40 43%
Male	24 57.1%	29 56.9%	53 57%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival at 6 Months
Description	The primary endpoint is the 6 month post registration Progression-free survival (PFS) rate. Progression-free survival time is defined as the time from registration to documentation of disease progression using the RECIST criteria. Patients who died without documentation of disease progression will be considered to have progressed at death unless there is sufficient documented evidence to conclude no progression occurred prior to death. All patients, who meet the eligibility criteria, sign a consent form, and start treatment will be included in the evaluation of the 6 month PFS rate.
Time Frame	at 6 months

Outcome Measure Data

Analysis Population Description

The first 41 eligible patients randomized to each treatment arm.

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15. > > bevacizumab: Given IV over 30-90 minutes > > temozolomide: Oral temozolomide on days 1-5	Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. > > bevacizumab: Given IV over 30-90 minutes > > carboplatin: Given IV over 30 minutes > > paclitaxel albumin-stabilized nanoparticle formulation: Given IV over 30 minutes
Measure Participants	41	41
Number (90% Confidence Interval) [% of patients alive and progression free]	32.8	56.1

2. Secondary Outcome

Title	Tumor Response Rate, Calculated as a Percentage Along With it's 95% Confidence Interval
Description	A confirmed tumor response is defined to be a Complete Response or Partial Response noted > as the objective status on 2 consecutive evaluations at least 8 > weeks apart. The proportion of tumor responses will be > estimated by the number of confirmed tumor responses divided > by the total number of evaluable patients. > Complete Response (CR): Disappearance of all target lesions > Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. > Progression (PD): At least a 20% increase in the sum of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. > Stable Disease (SD): Neither sufficient shrinkage to Qualify for PR nor sufficient increase to Qualify for PD taking as reference the smallest sum LD. responses will be calculated assuming that the number of > confirmed tumor responses follows a binomial distribution.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15. > > bevacizumab: Given IV over 30-90 minutes > > temozolomide: Oral temozolomide on days 1-5	Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. > > bevacizumab: Given IV over 30-90 minutes > > carboplatin: Given IV over 30 minutes > > paclitaxel albumin-stabilized nanoparticle formulation: Given IV over 30 minutes
Measure Participants	42	51
Number (95% Confidence Interval) [percentage of patients with response]	23.8	33.3

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm II
Arm/Group Description	Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15. > > bevacizumab: Given IV over 30-90 minutes > > temozolomide: Oral temozolomide on days 1-5	Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. > > bevacizumab: Given IV over 30-90 minutes > > carboplatin: Given IV over 30 minutes > > paclitaxel albumin-stabilized nanoparticle formulation: Given IV over 30 minutes
Measure Participants	42	51
Median (95% Confidence Interval) [Months]	12.3	13.9

Adverse Events

Time Frame	Until treatment discontinuation
Arm/Group Title	Arm I		Arm II
Arm/Group Description	temozolomide: Oral temozolomide on days 1-5		paclitaxel albumin-stabilized nanoparticle formulation: Given IV over 30 minutes
All Cause Mortality
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/43 (16.3%)		18/51 (35.3%)
Blood and lymphatic system disorders
Blood disorder	1/43 (2.3%)	1	0/51 (0%)	0
Febrile neutropenia	0/43 (0%)	0	1/51 (2%)	1
Hemoglobin decreased	2/43 (4.7%)	2	5/51 (9.8%)	5
Cardiac disorders
Arrhythmia	1/43 (2.3%)	1	0/51 (0%)	0
Gastrointestinal disorders
Diarrhea	0/43 (0%)	0	1/51 (2%)	1
Ileal obstruction	1/43 (2.3%)	1	0/51 (0%)	0
Intra-abdominal hemorrhage	1/43 (2.3%)	1	0/51 (0%)	0
Nausea	2/43 (4.7%)	2	1/51 (2%)	1
Pancreatitis	0/43 (0%)	0	1/51 (2%)	2
Vomiting	1/43 (2.3%)	1	0/51 (0%)	0
General disorders
Chest pain	0/43 (0%)	0	1/51 (2%)	1
Fatigue	2/43 (4.7%)	2	0/51 (0%)	0
Fever	1/43 (2.3%)	1	0/51 (0%)	0
Infections and infestations
Catheter related infection	0/43 (0%)	0	1/51 (2%)	1
Pneumonia	1/43 (2.3%)	1	1/51 (2%)	1
Urinary tract infection	1/43 (2.3%)	1	1/51 (2%)	1
Investigations
Leukocyte count decreased	2/43 (4.7%)	2	1/51 (2%)	1
Lymphocyte count decreased	0/43 (0%)	0	1/51 (2%)	1
Neutrophil count decreased	2/43 (4.7%)	2	7/51 (13.7%)	7
Platelet count decreased	3/43 (7%)	3	5/51 (9.8%)	5
Metabolism and nutrition disorders
Dehydration	1/43 (2.3%)	1	1/51 (2%)	1
Serum phosphate decreased	0/43 (0%)	0	1/51 (2%)	1
Serum sodium decreased	0/43 (0%)	0	1/51 (2%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	0/43 (0%)	0	1/51 (2%)	1
Nervous system disorders
Intracranial hemorrhage	1/43 (2.3%)	1	0/51 (0%)	0
Seizure	0/43 (0%)	0	1/51 (2%)	1
Renal and urinary disorders
Renal failure	0/43 (0%)	0	1/51 (2%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/43 (2.3%)	1	0/51 (0%)	0
Dyspnea	0/43 (0%)	0	3/51 (5.9%)	3
Hypoxia	0/43 (0%)	0	1/51 (2%)	1
Pleural effusion	0/43 (0%)	0	1/51 (2%)	2
Skin and subcutaneous tissue disorders
Rash acneiform	1/43 (2.3%)	1	0/51 (0%)	0
Vascular disorders
Hypertension	2/43 (4.7%)	2	0/51 (0%)	0
Hypotension	0/43 (0%)	0	1/51 (2%)	1
Thrombosis	0/43 (0%)	0	2/51 (3.9%)	2
Other (Not Including Serious) Adverse Events
	Arm I		Arm II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/43 (100%)		51/51 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	27/43 (62.8%)	79	46/51 (90.2%)	279
Eye disorders
Diplopia	0/43 (0%)	0	1/51 (2%)	1
Vision blurred	0/43 (0%)	0	1/51 (2%)	8
Gastrointestinal disorders
Abdominal distension	0/43 (0%)	0	1/51 (2%)	1
Abdominal pain	3/43 (7%)	4	3/51 (5.9%)	7
Constipation	2/43 (4.7%)	3	6/51 (11.8%)	10
Diarrhea	1/43 (2.3%)	1	2/51 (3.9%)	2
Dyspepsia	1/43 (2.3%)	2	2/51 (3.9%)	2
Esophageal stenosis	0/43 (0%)	0	1/51 (2%)	1
Esophageal varices hemorrhage	0/43 (0%)	0	1/51 (2%)	1
Hemorrhoids	0/43 (0%)	0	1/51 (2%)	1
Intra-abdominal hemorrhage	2/43 (4.7%)	4	4/51 (7.8%)	9
Mucositis oral	0/43 (0%)	0	3/51 (5.9%)	9
Nausea	32/43 (74.4%)	130	32/51 (62.7%)	94
Oral cavity fistula	0/43 (0%)	0	1/51 (2%)	1
Vomiting	20/43 (46.5%)	42	15/51 (29.4%)	37
General disorders
Disease progression	1/43 (2.3%)	1	1/51 (2%)	1
Edema limbs	0/43 (0%)	0	1/51 (2%)	1
Fatigue	42/43 (97.7%)	207	48/51 (94.1%)	254
Fever	9/43 (20.9%)	10	8/51 (15.7%)	8
Immune system disorders
Hypersensitivity	3/43 (7%)	5	5/51 (9.8%)	7
Infections and infestations
Infection	0/43 (0%)	0	2/51 (3.9%)	2
Pleural infection	1/43 (2.3%)	1	0/51 (0%)	0
Pneumonia	0/43 (0%)	0	1/51 (2%)	1
Scrotal infection	0/43 (0%)	0	1/51 (2%)	1
Sinusitis	0/43 (0%)	0	1/51 (2%)	1
Skin infection	0/43 (0%)	0	1/51 (2%)	1
Urinary tract infection	0/43 (0%)	0	3/51 (5.9%)	3
Injury, poisoning and procedural complications
Wound dehiscence	1/43 (2.3%)	1	3/51 (5.9%)	4
Investigations
Alanine aminotransferase increased	0/43 (0%)	0	1/51 (2%)	1
Alkaline phosphatase increased	2/43 (4.7%)	2	0/51 (0%)	0
Aspartate aminotransferase increased	1/43 (2.3%)	1	0/51 (0%)	0
Bilirubin increased	0/43 (0%)	0	1/51 (2%)	1
Leukocyte count decreased	15/43 (34.9%)	45	38/51 (74.5%)	191
Lymphocyte count decreased	0/43 (0%)	0	4/51 (7.8%)	11
Neutrophil count decreased	7/43 (16.3%)	8	36/51 (70.6%)	159
Platelet count decreased	17/43 (39.5%)	64	30/51 (58.8%)	145
Weight loss	0/43 (0%)	0	5/51 (9.8%)	10
Metabolism and nutrition disorders
Anorexia	4/43 (9.3%)	4	7/51 (13.7%)	13
Blood glucose increased	0/43 (0%)	0	3/51 (5.9%)	6
Dehydration	4/43 (9.3%)	4	4/51 (7.8%)	4
Serum albumin decreased	0/43 (0%)	0	1/51 (2%)	1
Serum calcium decreased	0/43 (0%)	0	2/51 (3.9%)	2
Serum magnesium decreased	0/43 (0%)	0	1/51 (2%)	1
Serum potassium decreased	1/43 (2.3%)	1	1/51 (2%)	1
Serum sodium decreased	1/43 (2.3%)	1	1/51 (2%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/43 (2.3%)	2	3/51 (5.9%)	7
Bone pain	1/43 (2.3%)	1	1/51 (2%)	1
Chest wall pain	2/43 (4.7%)	2	0/51 (0%)	0
Joint pain	17/43 (39.5%)	69	20/51 (39.2%)	74
Muscle weakness	1/43 (2.3%)	1	0/51 (0%)	0
Myalgia	21/43 (48.8%)	66	18/51 (35.3%)	54
Pain in extremity	2/43 (4.7%)	2	1/51 (2%)	1
Trismus	0/43 (0%)	0	1/51 (2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/43 (2.3%)	1	2/51 (3.9%)	4
Nervous system disorders
Acoustic nerve disorder NOS	0/43 (0%)	0	1/51 (2%)	1
Ataxia	0/43 (0%)	0	1/51 (2%)	1
Dizziness	2/43 (4.7%)	2	0/51 (0%)	0
Encephalopathy	0/43 (0%)	0	1/51 (2%)	1
Headache	1/43 (2.3%)	2	3/51 (5.9%)	14
Intracranial hemorrhage	0/43 (0%)	0	2/51 (3.9%)	2
Memory impairment	0/43 (0%)	0	1/51 (2%)	5
Peripheral motor neuropathy	1/43 (2.3%)	1	1/51 (2%)	1
Peripheral sensory neuropathy	10/43 (23.3%)	16	24/51 (47.1%)	85
Sinus pain	0/43 (0%)	0	1/51 (2%)	2
Speech disorder	0/43 (0%)	0	1/51 (2%)	1
Taste alteration	0/43 (0%)	0	2/51 (3.9%)	7
Psychiatric disorders
Anxiety	0/43 (0%)	0	1/51 (2%)	1
Confusion	0/43 (0%)	0	1/51 (2%)	1
Depression	1/43 (2.3%)	1	1/51 (2%)	1
Insomnia	1/43 (2.3%)	1	1/51 (2%)	1
Renal and urinary disorders
Protein urine positive	14/43 (32.6%)	29	19/51 (37.3%)	73
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/43 (2.3%)	1	0/51 (0%)	0
Aspiration	0/43 (0%)	0	1/51 (2%)	1
Bronchopulmonary hemorrhage	8/43 (18.6%)	20	15/51 (29.4%)	41
Bronchospasm	0/43 (0%)	0	1/51 (2%)	1
Dyspnea	2/43 (4.7%)	2	6/51 (11.8%)	11
Hemorrhage nasal	2/43 (4.7%)	2	0/51 (0%)	0
Hypoxia	0/43 (0%)	0	1/51 (2%)	1
Pleural effusion	0/43 (0%)	0	1/51 (2%)	1
Pneumonitis	0/43 (0%)	0	1/51 (2%)	1
Voice alteration	0/43 (0%)	0	1/51 (2%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/43 (0%)	0	6/51 (11.8%)	19
Dry skin	0/43 (0%)	0	1/51 (2%)	1
Nail disorder	0/43 (0%)	0	2/51 (3.9%)	2
Pruritus	0/43 (0%)	0	1/51 (2%)	1
Rash desquamating	2/43 (4.7%)	3	0/51 (0%)	0
Skin ulceration	1/43 (2.3%)	1	1/51 (2%)	1
Vascular disorders
Hypertension	23/43 (53.5%)	62	18/51 (35.3%)	59
Thrombosis	3/43 (7%)	4	5/51 (9.8%)	7

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.