S0802 - Topotecan With or Without Aflibercept in Treating Patients With Extensive-Stage Small Cell Lung Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00828139
• Collaborator: (none)
• Enrollment: 189
• Locations: 257
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial is studying topotecan to see how well it works when given with or without aflibercept in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Combinations of biological substances in aflibercept may be able to carry tumor-killing substances directly to small cell lung cancer cells. Aflibercept may also stop the growth of small cell lung cancer by blocking blood flow to the tumor. It is not yet known whether topotecan is more effective with or without aflibercept in treating patients with small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer	Biological: ziv-aflibercept; Drug: topotecan hydrochloride	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate the efficacy of topotecan hydrochloride with vs without aflibercept (ziv-aflibercept), in terms of progression-free survival at 3 months, in patients with extensive stage small cell lung cancer previously treated with platinum-based therapy.

SECONDARY OBEJCTIVES:

1. Assess the response rate (confirmed and unconfirmed, complete and partial responses) in a subset of patients with measurable disease.

2. Assess the overall survival of these patients. III. Evaluate the frequency and severity of toxicities of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to response to prior platinum-based therapy (platinum-sensitive disease vs platinum-refractory disease). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive ziv-aflibercept IV over 1 hour on day 1 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive ziv-aflibercept IV on day 1 and topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Weekly Topotecan With and Without AVE0005 (Aflibercept; NSC-724770) in Patients With Platinum Treated Extensive Stage Small Cell Lung Cancer (E-SCLC)
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (ziv-aflibercept, topotecan hydrochloride) Patients receive ziv-aflibercept IV over 1 hour on day 1 and topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive ziv-aflibercept IV on day 1 and topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: ziv-aflibercept; Given IV; Other Names: aflibercept vascular endothelial growth factor trap VEGF Trap Zaltrap ; Drug: topotecan hydrochloride; Given IV; Other Names: hycamptamine Hycamtin SKF S-104864-A TOPO
Active Comparator: Arm II (topotecan hydrochloride) Patients receive topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease after 4 courses may then receive topotecan hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: topotecan hydrochloride; Given IV; Other Names: hycamptamine Hycamtin SKF S-104864-A TOPO

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Disease assessments were performed every 6 weeks, up to 2 years.]

   From the date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined as 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.

Secondary Outcome Measures

1. Overall Survival [Weekly, up to 2 years.]

   Estimated to within at least 15% (95% confidence interval).

2. Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses) [Disease assessment for response were performed every 6 weeks, up to 2 years.]

   The number of confirmed and unconfirmed complete and partial responses in the subset of patients with measurable disease per RECIST 1.0. Estimated to within at least 17% (95% confidence interval). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

3. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs [Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.]

   Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. The events listed here are not necessary to be included in Serious Adverse Event. A serious event could be death, life-threatening, hospitalization, disability or permanent damage, congenital anomaly...Grade 3 through 5 adverse event may not meet the criterion of serious adverse event.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed extensive stage small cell lung cancer

• Progressive or recurrent disease following one (and only one) standard first-line platinum-containing regimen (cisplatin or carboplatin)

• Measurable or non-measurable disease per RECIST criteria

• Disease must be outside a previously irradiated field OR a new lesion must be inside the irradiated field

• Disease must be outside a previously resected area OR a new lesion must be present

• No known brain metastasis unless the metastasis has been treated and is stable for ≥ 3 months prior to study entry

• No leptomeningeal involvement or brain stem metastasis

• Zubrod performance status 0-1

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 10 g/dL

• Serum creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min

• Urine protein: creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Willing to provide smoking history

• No evidence of active infection

• No active bleeding

• No significant history of bleeding diathesis, including hemoptysis (½ teaspoon of hemoptysis within the past 3 months), or underlying coagulopathy

• No history of recent arterial embolic events, including any of the following:

• Myocardial infarction

• Cerebrovascular accident

• Transient ischemic attack

• Worsening of pre-existing angina within the past 6 months

• No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg)

• History of hypertension allowed provided it is controlled on anti-hypertensive medications

• No history of congestive heart failure

• No history of encephalitis or encephalopathy of any cause

• No diverticulitis, gastrointestinal bleeding, or peptic ulcer within the past 3 months

• No known AIDS or HIV-1 associated complex

• No known history of immune or immunodeficiency disorders

• No unstable or pre-existing major medical conditions except for cancer-related abnormalities

• No other prior malignancy 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 currently in complete remission

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

• Concurrent chronic therapeutic doses of low molecular weight heparin allowed

• At least 21 days since prior and no concurrent radiotherapy and recovered

• At least 28 days since prior and no concurrent surgery (e.g., thoracic or other major surgeries) and recovered

• No prior bevacizumab or other anti-angiogenic therapies including, but not limited to, small molecule tyrosine kinase inhibitors

• No concurrent enzyme-inducing anticonvulsant drugs

• Non-enzyme-inducing anticonvulsant drugs (e.g., Keppra) allowed

• Concurrent chronic oral anticoagulation therapy allowed provided INR is maintained in the therapeutic range (INR 2-3)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Alabama Regional Medical Center	Anniston	Alabama	United States	36202
2	Providence Hospital	Mobile	Alabama	United States	36608
3	Arizona Cancer Center at UMC Orange Grove	Tucson	Arizona	United States	85704
4	Arizona Cancer Center at University Medical Center North	Tucson	Arizona	United States	85719
5	University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724
6	NEA Baptist Memorial Hospital	Jonesboro	Arkansas	United States	72401
7	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
8	Highlands Oncology Group-Rogers	Rogers	Arkansas	United States	72758
9	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
10	Eden Hospital Medical Center	Castro Valley	California	United States	94546
11	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
12	City of Hope Medical Center	Duarte	California	United States	91010
13	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
14	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
15	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
16	El Camino Hospital	Mountain View	California	United States	94040
17	Highland General Hospital	Oakland	California	United States	94602
18	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
19	Bay Area Breast Surgeons Inc	Oakland	California	United States	94609
20	Bay Area Tumor Institute CCOP	Oakland	California	United States	94609
21	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
22	Tom K Lee Inc	Oakland	California	United States	94609
23	Valley Care Health System - Pleasanton	Pleasanton	California	United States	94588
24	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
25	University of California at Davis Cancer Center	Sacramento	California	United States	95817
26	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
27	San Luis Valley Regional Medical Center	Alamosa	Colorado	United States	81101
28	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
29	The Shaw Regional Cancer Center	Edwards	Colorado	United States	81632
30	Valley View Hospital Cancer Center	Glenwood Springs	Colorado	United States	81601
31	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
32	Montrose Memorial Hospital	Montrose	Colorado	United States	81401
33	Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
34	Piedmont Hospital	Atlanta	Georgia	United States	30309
35	Atlanta Regional CCOP	Atlanta	Georgia	United States	30342
36	Northside Hospital	Atlanta	Georgia	United States	30342
37	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342
38	Well Star Cobb Hospital	Austell	Georgia	United States	30106
39	John B Amos Cancer Center	Columbus	Georgia	United States	31904
40	Dekalb Medical Center	Decatur	Georgia	United States	30033
41	Piedmont Fayette Hospital	Fayetteville	Georgia	United States	30214
42	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
43	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
44	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
45	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia	United States	30165
46	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
47	South Georgia Medical Center	Valdosta	Georgia	United States	31603
48	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
49	Saint Anthony's Health	Alton	Illinois	United States	62002
50	Cancer Care Center of Decatur	Decatur	Illinois	United States	62526
51	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
52	Loyola University Medical Center	Maywood	Illinois	United States	60153
53	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
54	Memorial Medical Center	Springfield	Illinois	United States	62781-0001
55	Saint Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
56	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
57	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
58	Genesis Medical Center - West Campus	Davenport	Iowa	United States	52804
59	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
60	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
61	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
62	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
63	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
64	Hays Medical Center	Hays	Kansas	United States	67601
65	Promise Regional Medical Center-Hutchinson	Hutchinson	Kansas	United States	65702
66	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
67	Kansas City Cancer Center-West	Kansas City	Kansas	United States	66112
68	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
69	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
70	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
71	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67901
72	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
73	Olathe Cancer Center	Olathe	Kansas	United States	66061
74	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
75	Via Christi Hospital-Pittsburg	Pittsburg	Kansas	United States	66762
76	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
77	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
78	Salina Regional Health Center	Salina	Kansas	United States	67401
79	Stormont-Vail Regional Health Center	Topeka	Kansas	United States	66604
80	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas	United States	66606
81	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
82	Associates In Womens Health	Wichita	Kansas	United States	67208
83	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
84	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
85	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
86	Wichita CCOP	Wichita	Kansas	United States	67214
87	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
88	University of Kentucky	Lexington	Kentucky	United States	40536
89	Baton Rouge General Medical Center	Baton Rouge	Louisiana	United States	70806
90	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
91	Interim LSU Public Hospital	New Orleans	Louisiana	United States	70112
92	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
93	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
94	Boston Medical Center	Boston	Massachusetts	United States	02118
95	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
96	Holy Family Hospital	Methuen	Massachusetts	United States	01844
97	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
98	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan	United States	48106
99	University of Michigan	Ann Arbor	Michigan	United States	48109
100	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
101	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
102	Oakwood Hospital	Dearborn	Michigan	United States	48124
103	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
104	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
105	Hurley Medical Center	Flint	Michigan	United States	48502
106	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
107	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
108	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
109	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
110	Allegiance Health	Jackson	Michigan	United States	49201
111	Sparrow Hospital	Lansing	Michigan	United States	48912
112	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
113	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
114	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
115	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
116	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
117	Munson Medical Center	Traverse City	Michigan	United States	49684
118	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
119	Metro Health Hospital	Wyoming	Michigan	United States	49519
120	Gulfport Memorial Hospital	Gulfport	Mississippi	United States	39502
121	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
122	Singing River Hospital	Pascagoula	Mississippi	United States	39581
123	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
124	Truman Medical Center	Kansas City	Missouri	United States	64108
125	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
126	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
127	Saint Louis University Hospital	Saint Louis	Missouri	United States	63110
128	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
129	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
130	Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield	Springfield	Missouri	United States	65802
131	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
132	CoxHealth South Hospital	Springfield	Missouri	United States	65807
133	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
134	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
135	Saint Vincent Healthcare	Billings	Montana	United States	59101
136	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana	United States	59102
137	Billings Clinic	Billings	Montana	United States	59107-7000
138	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
139	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
140	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
141	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
142	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
143	Big Sky Oncology	Great Falls	Montana	United States	59405
144	Great Falls Clinic	Great Falls	Montana	United States	59405
145	Northern Montana Hospital	Havre	Montana	United States	59501
146	Saint Peter's Community Hospital	Helena	Montana	United States	59601
147	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
148	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
149	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
150	Community Medical Hospital	Missoula	Montana	United States	59801
151	Montana Cancer Specialists	Missoula	Montana	United States	59802
152	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
153	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
154	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
155	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
156	Arnot Ogden Medical Center	Elmira	New York	United States	14905
157	Adirondack Cancer Center	Glens Falls	New York	United States	12801
158	Winthrop University Hospital	Mineola	New York	United States	11501
159	Columbia University Medical Center	New York	New York	United States	10032
160	Highland Hospital	Rochester	New York	United States	14620
161	Interlakes Foundation Inc-Rochester	Rochester	New York	United States	14623
162	University of Rochester	Rochester	New York	United States	14642
163	Randolph Hospital	Asheboro	North Carolina	United States	27203
164	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
165	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
166	Carolinas Medical Center - Northeast	Concord	North Carolina	United States	28025
167	Gaston Memorial Hospital	Gastonia	North Carolina	United States	28054
168	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
169	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
170	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
171	High Point Regional Hospital	High Point	North Carolina	United States	27261
172	Annie Penn Memorial Hospital	Reidsville	North Carolina	United States	27320
173	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
174	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
175	Akron General Medical Center	Akron	Ohio	United States	44307
176	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
177	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
178	University of Cincinnati	Cincinnati	Ohio	United States	45267
179	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
180	Columbus CCOP	Columbus	Ohio	United States	43215
181	Grant Medical Center	Columbus	Ohio	United States	43215
182	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
183	Doctors Hospital	Columbus	Ohio	United States	43228
184	Grandview Hospital	Dayton	Ohio	United States	45405
185	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
186	Miami Valley Hospital	Dayton	Ohio	United States	45409
187	Samaritan North Health Center	Dayton	Ohio	United States	45415
188	Dayton CCOP	Dayton	Ohio	United States	45420
189	Grady Memorial Hospital	Delaware	Ohio	United States	43015
190	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
191	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
192	Wayne Hospital	Greenville	Ohio	United States	45331
193	Kettering Medical Center	Kettering	Ohio	United States	45429
194	Fairfield Medical Center	Lancaster	Ohio	United States	43130
195	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
196	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
197	Licking Memorial Hospital	Newark	Ohio	United States	43055
198	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
199	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
200	Upper Valley Medical Center	Troy	Ohio	United States	45373
201	Saint Ann's Hospital	Westerville	Ohio	United States	43081
202	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
203	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
204	Greene Memorial Hospital	Xenia	Ohio	United States	45385
205	Genesis HealthCare System	Zanesville	Ohio	United States	43701
206	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
207	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
208	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
209	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
210	Providence Portland Medical Center	Portland	Oregon	United States	97213
211	Western Oncology Research Consortium	Portland	Oregon	United States	97213
212	Adventist Medical Center	Portland	Oregon	United States	97216
213	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
214	Oregon Health and Science University	Portland	Oregon	United States	97239
215	Salem Hospital	Salem	Oregon	United States	97301
216	AnMed Health Hospital	Anderson	South Carolina	United States	29621
217	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
218	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
219	Upstate Carolina CCOP	Spartanburg	South Carolina	United States	29303
220	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
221	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee	United States	38104
222	University of Tennessee - Memphis	Memphis	Tennessee	United States	38163
223	University of Texas Medical Branch at Galveston	Galveston	Texas	United States	77555-0565
224	Baylor College of Medicine	Houston	Texas	United States	77030
225	Ben Taub General Hospital	Houston	Texas	United States	77030
226	Methodist Hospital	Houston	Texas	United States	77030
227	Saint Luke's Episcopal Hospital	Houston	Texas	United States	77030
228	Veterans Administration Medical Center	Houston	Texas	United States	77030
229	Texas Tech University Health Sciences Center	Lubbock	Texas	United States	79430
230	Southwest Oncology Group	San Antonio	Texas	United States	78245
231	Scott and White Memorial Hospital	Temple	Texas	United States	76508
232	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
233	Danville Regional Medical Center	Danville	Virginia	United States	24541
234	Memorial Hospital Of Martinsville	Martinsville	Virginia	United States	24115
235	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
236	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
237	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
238	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
239	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington	United States	99336
240	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
241	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
242	Harborview Medical Center	Seattle	Washington	United States	98104
243	Minor and James Medical PLLC	Seattle	Washington	United States	98104
244	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
245	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
246	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
247	The Polyclinic	Seattle	Washington	United States	98122
248	University of Washington Medical Center	Seattle	Washington	United States	98195
249	United General Hospital	Sedro-Woolley	Washington	United States	98284
250	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
251	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
252	Rockwood Clinic	Spokane	Washington	United States	99220
253	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
254	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
255	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801
256	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
257	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jeffrey Allen, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00828139
• Other Study ID Numbers: NCI-2009-01182; NCI-2009-01182; SWOG-S0802; CDR0000632614; S0802; S0802
• First Posted: Jan 23, 2009
• Last Update Posted: Aug 21, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Aflibercept; Topotecan; Endothelial Growth Factors

Study Results

Participant Flow

Arm/Group Title	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept	Platinum Sensitivity Treated With Topotecan Alone	Platinum Refractory Treated With Topotecan + Ziv-aflibercept	Platinum Refractory Treated With Topotecan Aloine
Arm/Group Description	Patients with platinum sensitive (complete response or partial response and > 90 day treatment-free interval for extensive stage or ≥ 180 days for limited stage) were treated with Topotecan and ziv-aflibercept.	Patients with platinum sensitivity treated with topotecan alone	Patients with platinum refractory (no response and/or treatment-free interval ≤ 90 days for extensive stage and < 180 days for limited stage) treated topotecan and ziv-aflibercept.	Patients with platinum refractory treated topotecan alone.
Period Title: Overall Study
STARTED	42	41	55	51
COMPLETED	1	0	0	0
NOT COMPLETED	41	41	55	51

Baseline Characteristics

Arm/Group Title	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept	Platinum Sensitivity Treated With Topotecan Alone	Platinum Refractory Treated With Topotecan + Ziv-aflibercept	Platinum Refractory Treated With Topotecan Aloine	Total
Arm/Group Description	Patients with platinum sensitive (complete response or partial response and > 90 day treatment-free interval for extensive stage or ≥ 180 days for limited stage) were treated with Topotecan and ziv-aflibercept.	Patients with platinum sensitivity treated with topotecan alone	Patients with platinum refractory (no response and/or treatment-free interval ≤ 90 days for extensive stage and < 180 days for limited stage) treated topotecan and ziv-aflibercept.	Patients with platinum refractory treated topotecan alone.	Total of all reporting groups
Overall Participants	42	41	55	51	189
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.4	60.1	60.9	63.6	62.5
Sex: Female, Male (Count of Participants)
Female	25 59.5%	28 68.3%	29 52.7%	17 33.3%	99 52.4%
Male	17 40.5%	13 31.7%	26 47.3%	34 66.7%	90 47.6%
Race/Ethnicity, Customized (participants) [Number]
White	36 85.7%	40 97.6%	49 89.1%	43 84.3%	168 88.9%
Black	4 9.5%	1 2.4%	3 5.5%	4 7.8%	12 6.3%
Pacific Islander	1 2.4%	0 0%	0 0%	0 0%	1 0.5%
Asian	0 0%	0 0%	0 0%	1 2%	1 0.5%
Native American	0 0%	0 0%	2 3.6%	1 2%	3 1.6%
Unknown/Other	1 2.4%	0 0%	1 1.8%	2 3.9%	4 2.1%
Metastatic Disease Sites (participants) [Number]
Single lesion, single organ	4 9.5%	9 22%	4 7.3%	4 7.8%	21 11.1%
Multiple lesions, single organ	11 26.2%	9 22%	9 16.4%	11 21.6%	40 21.2%
Multiple lesions, multiple organs	25 59.5%	22 53.7%	41 74.5%	34 66.7%	122 64.6%
None	2 4.8%	1 2.4%	1 1.8%	2 3.9%	6 3.2%
Stage (participants) [Number]
Extensive	27 64.3%	23 56.1%	39 70.9%	42 82.4%	131 69.3%
Limited	15 35.7%	18 43.9%	16 29.1%	9 17.6%	58 30.7%
Performance Status (participants) [Number]
0	14 33.3%	17 41.5%	12 21.8%	19 37.3%	62 32.8%
1	28 66.7%	24 58.5%	43 78.2%	32 62.7%	127 67.2%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	From the date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined as 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration.
Time Frame	Disease assessments were performed every 6 weeks, up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept	Platinum Sensitivity Treated With Topotecan Alone	Platinum Refractory Treated With Topotecan + Ziv-aflibercept	Platinum Refractory Treated With Topotecan Aloine
Arm/Group Description	Patients with platinum sensitive (complete response or partial response and > 90 day treatment-free interval for extensive stage or ≥ 180 days for limited stage) were treated with Topotecan and ziv-aflibercept.	Patients with platinum sensitivity treated with topotecan alone	Patients with platinum refractory (no response and/or treatment-free interval ≤ 90 days for extensive stage and < 180 days for limited stage) treated topotecan and ziv-aflibercept.	Patients with platinum refractory treated topotecan alone.
Measure Participants	42	41	55	51
Median (90% Confidence Interval) [Months]	1.8	1.3	1.4	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept
	Comments	3-month PFS was estimated using the method of Kaplan-Meier. The 3-month PFS estimated value corresponds to the probability of PFS at month 3.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	3-month PFS
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 90%; 0.14 to 0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value corresponds to the probability of PFS at month 3.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Platinum Sensitivity Treated With Topotecan Alone
	Comments	3-month PFS was estimated using the method of Kaplan-Meier.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	3-month PFS
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 90%; 0.07 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value corresponds to the probability of PFS at month 3.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Platinum Refractory Treated With Topotecan + Ziv-aflibercept
	Comments	3-month PFS was estimated using the method of Kaplan-Meier.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	3-month PFS
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 90%; 0.18 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value corresponds to the probability of PFS at month 3.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Platinum Refractory Treated With Topotecan Aloine
	Comments	3-month PFS was estimated using the method of Kaplan-Meier.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	3-month PFS
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 90%; 0.04 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value corresponds to the probability of PFS at month 3.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept, Platinum Sensitivity Treated With Topotecan Alone
	Comments	Hazard Ratio was evaluated using a logrank test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 90%; 0.91 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Platinum Refractory Treated With Topotecan + Ziv-aflibercept, Platinum Refractory Treated With Topotecan Aloine
	Comments	Hazard Ratio was evaluated using log-rank test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 90%; 1.08 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival
Description	Estimated to within at least 15% (95% confidence interval).
Time Frame	Weekly, up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept	Platinum Sensitivity Treated With Topotecan Alone	Platinum Refractory Treated With Topotecan + Ziv-aflibercept	Platinum Refractory Treated With Topotecan Aloine
Arm/Group Description	Patients with platinum sensitive (complete response or partial response and > 90 day treatment-free interval for extensive stage or ≥ 180 days for limited stage) were treated with Topotecan and ziv-aflibercept.	Patients with platinum sensitivity treated with topotecan alone	Patients with platinum refractory (no response and/or treatment-free interval ≤ 90 days for extensive stage and < 180 days for limited stage) treated topotecan and ziv-aflibercept.	Patients with platinum refractory treated topotecan alone.
Measure Participants	42	41	55	51
Median (90% Confidence Interval) [months]	6.0	4.6	4.6	4.2

3. Secondary Outcome

Title	Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses)
Description	The number of confirmed and unconfirmed complete and partial responses in the subset of patients with measurable disease per RECIST 1.0. Estimated to within at least 17% (95% confidence interval). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Disease assessment for response were performed every 6 weeks, up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Platinum-Sensitive Treated With Topotecan and Ziv-aflibercept	Platinum Sensitivity Treated With Topotecan Alone	Platinum Refractory Treated With Topotecan + Ziv-aflibercept	Platinum Refractory Treated With Topotecan Aloine
Arm/Group Description	Patients with platinum sensitive (complete response or partial response and > 90 day treatment-free interval for extensive stage or ≥ 180 days for limited stage) were treated with Topotecan and ziv-aflibercept.	Patients with platinum sensitivity treated with topotecan alone	Patients with platinum refractory (no response and/or treatment-free interval ≤ 90 days for extensive stage and < 180 days for limited stage) treated topotecan and ziv-aflibercept.	Patients with platinum refractory treated topotecan alone.
Measure Participants	41	39	51	48
Number (90% Confidence Interval) [proportion of participants]	0.02 0%	0 0%	0.02 0%	0 0%

4. Secondary Outcome

Title	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. The events listed here are not necessary to be included in Serious Adverse Event. A serious event could be death, life-threatening, hospitalization, disability or permanent damage, congenital anomaly...Grade 3 through 5 adverse event may not meet the criterion of serious adverse event.
Time Frame	Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.

Outcome Measure Data

Analysis Population Description

Eligible patients who had received the protocol treatments were included in the adverse event summaries. Ant CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Arm/Group Title	Ziv-aflibercept + Topotecan	Topotecan
Arm/Group Description
Measure Participants	92	87
AST, SGOT	1 2.4%	2 4.9%
Anorexia	3 7.1%	2 4.9%
Bilirubin (hyperbilirubinemia)	1 2.4%	0 0%
Bronchospasm, wheezing	0 0%	1 2.4%
Calcium, serum-high (hypercalcemia)	1 2.4%	0 0%
Cardiac-ischemia/infarction	1 2.4%	0 0%
Colitis, infectious (e.g., Clostridium difficile)	1 2.4%	0 0%
Confusion	3 7.1%	0 0%
Constipation	0 0%	1 2.4%
Creatinine	0 0%	1 2.4%
Dehydration	6 14.3%	1 2.4%
Diarrhea	1 2.4%	0 0%
Dizziness	2 4.8%	1 2.4%
Dyspnea (shortness of breath)	7 16.7%	1 2.4%
Fatigue (asthenia, lethargy, malaise)	15 35.7%	3 7.3%
Febrile neutropenia	1 2.4%	0 0%
GGT (gamma-glutamyl transpeptidase)	1 2.4%	0 0%
Hemoglobin	9 21.4%	7 17.1%
Hemolysis	1 2.4%	1 2.4%
Hemorrhage, GI - Upper GI NOS	2 4.8%	0 0%
Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS	1 2.4%	0 0%
Hemorrhage, pulmonary/upper respiratory - Lung	1 2.4%	0 0%
Hemorrhage, pulmonary/upper respiratory - Nose	2 4.8%	0 0%
Hypertension	3 7.1%	0 0%
INR (of prothrombin time)	1 2.4%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Colon	1 2.4%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	0 0%	1 2.4%
Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus	1 2.4%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	1 2.4%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	0 0%	1 2.4%
Infection with unknown ANC - Blood	0 0%	2 4.9%
Infection with unknown ANC - Lung (pneumonia)	1 2.4%	0 0%
Left ventricular systolic dysfunction	1 2.4%	0 0%
Leukocytes (total WBC)	17 40.5%	22 53.7%
Leukoencephalopathy (radiolographic findings)	1 2.4%	0 0%
Lipase	1 2.4%	0 0%
Lymphopenia	5 11.9%	13 31.7%
Mucositis/stomatitis (clinical exam) - Oral cavity	1 2.4%	0 0%
Muscle weakness, not d/t neuropathy - body/general	3 7.1%	1 2.4%
Nausea	4 9.5%	1 2.4%
Neutrophils/granulocytes (ANC/AGC)	30 71.4%	23 56.1%
Pain - Abdomen NOS	3 7.1%	0 0%
Pain - Chest wall	1 2.4%	0 0%
Pain - Head/headache	2 4.8%	0 0%
Pain - Pain NOS	1 2.4%	0 0%
Platelets	29 69%	17 41.5%
Pneumonitis/pulmonary infiltrates	0 0%	1 2.4%
Potassium, serum-high (hyperkalemia)	0 0%	1 2.4%
Potassium, serum-low (hypokalemia)	3 7.1%	1 2.4%
Proteinuria	1 2.4%	0 0%
Psychosis (hallucinations/delusions)	0 0%	1 2.4%
Renal failure	0 0%	2 4.9%
Seizure	1 2.4%	0 0%
Sodium, serum-high (hypernatremia)	0 0%	1 2.4%
Sodium, serum-low (hyponatremia)	6 14.3%	1 2.4%
Syndromes-Other (Specify)	1 2.4%	0 0%
Thrombosis/thrombus/embolism	2 4.8%	0 0%
Voice changes/dysarthria	1 2.4%	0 0%
Vomiting	2 4.8%	0 0%
Weight loss	1 2.4%	0 0%

Adverse Events

Time Frame	Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.
Adverse Event Reporting Description	Only patients with measurable disease at baseline will be included in this analysis.
Arm/Group Title	Ziv-aflibercept + Topotecan		Topotecan
Arm/Group Description	There are total 97 patients in this arm, but only 92 patients with measurable disease at baseline will be included in this analysis.		There are total 92 patients in this arm, but only 87 patients with measurable disease at baseline will be included in this analysis.
All Cause Mortality
	Ziv-aflibercept + Topotecan		Topotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziv-aflibercept + Topotecan		Topotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/92 (47.8%)		17/87 (19.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/92 (1.1%)		0/87 (0%)
Hemoglobin	3/92 (3.3%)		1/87 (1.1%)
Hemolysis	1/92 (1.1%)		0/87 (0%)
Cardiac disorders
Cardiac General-Other	0/92 (0%)		1/87 (1.1%)
Cardiac-ischemia/infarction	1/92 (1.1%)		0/87 (0%)
Left ventricular systolic dysfunction	1/92 (1.1%)		0/87 (0%)
SVT and nodal arrhythmia - Atrial flutter	1/92 (1.1%)		0/87 (0%)
SVT and nodal arrhythmia - Sinus tachycardia	2/92 (2.2%)		0/87 (0%)
Gastrointestinal disorders
Colitis	1/92 (1.1%)		0/87 (0%)
Hemorrhage, GI - Upper GI NOS	2/92 (2.2%)		0/87 (0%)
Nausea	2/92 (2.2%)		0/87 (0%)
Pancreatitis	1/92 (1.1%)		0/87 (0%)
Vomiting	1/92 (1.1%)		0/87 (0%)
General disorders
Death not associated with CTCAE term - Death NOS	6/92 (6.5%)		3/87 (3.4%)
Fatigue (asthenia, lethargy, malaise)	5/92 (5.4%)		0/87 (0%)
Pain - Pain NOS	3/92 (3.3%)		0/87 (0%)
Syndromes-Other	1/92 (1.1%)		0/87 (0%)
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	1/92 (1.1%)		0/87 (0%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	1/92 (1.1%)		0/87 (0%)
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1/92 (1.1%)		0/87 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter	1/92 (1.1%)		0/87 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	2/92 (2.2%)		0/87 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	0/92 (0%)		1/87 (1.1%)
Infection with unknown ANC - Blood	0/92 (0%)		1/87 (1.1%)
Infection with unknown ANC - Lung (pneumonia)	1/92 (1.1%)		0/87 (0%)
Investigations
AST, SGOT	1/92 (1.1%)		0/87 (0%)
Bilirubin (hyperbilirubinemia)	1/92 (1.1%)		0/87 (0%)
Creatinine	1/92 (1.1%)		0/87 (0%)
GGT (gamma-glutamyl transpeptidase)	1/92 (1.1%)		0/87 (0%)
Neutrophils/granulocytes (ANC/AGC)	4/92 (4.3%)		0/87 (0%)
Platelets	8/92 (8.7%)		0/87 (0%)
Metabolism and nutrition disorders
Anorexia	2/92 (2.2%)		0/87 (0%)
Calcium, serum-high (hypercalcemia)	1/92 (1.1%)		0/87 (0%)
Dehydration	6/92 (6.5%)		0/87 (0%)
Potassium, serum-high (hyperkalemia)	2/92 (2.2%)		0/87 (0%)
Potassium, serum-low (hypokalemia)	1/92 (1.1%)		0/87 (0%)
Sodium, serum-low (hyponatremia)	3/92 (3.3%)		0/87 (0%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	3/92 (3.3%)		0/87 (0%)
Pain - Back	4/92 (4.3%)		0/87 (0%)
Pain - Chest wall	1/92 (1.1%)		0/87 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	8/92 (8.7%)		8/87 (9.2%)
Tumor flare	1/92 (1.1%)		0/87 (0%)
Nervous system disorders
Dizziness	2/92 (2.2%)		0/87 (0%)
Leukoencephalopathy (radiolographic findings)	1/92 (1.1%)		0/87 (0%)
Pain - Head/headache	1/92 (1.1%)		0/87 (0%)
Seizure	1/92 (1.1%)		0/87 (0%)
Psychiatric disorders
Confusion	4/92 (4.3%)		0/87 (0%)
Renal and urinary disorders
Renal failure	0/92 (0%)		1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	6/92 (6.5%)		1/87 (1.1%)
Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS	1/92 (1.1%)		0/87 (0%)
Hemorrhage, pulmonary/upper respiratory - Lung	1/92 (1.1%)		0/87 (0%)
Hemorrhage, pulmonary/upper respiratory - Nose	1/92 (1.1%)		0/87 (0%)
Hypoxia	1/92 (1.1%)		0/87 (0%)
Pleural effusion (non-malignant)	2/92 (2.2%)		0/87 (0%)
Pneumonitis/pulmonary infiltrates	1/92 (1.1%)		1/87 (1.1%)
Pulmonary/Upper Respiratory-Other	0/92 (0%)		1/87 (1.1%)
Vascular disorders
Hypertension	1/92 (1.1%)		0/87 (0%)
Thrombosis/thrombus/embolism	2/92 (2.2%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Ziv-aflibercept + Topotecan		Topotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/92 (98.9%)		86/87 (98.9%)
Blood and lymphatic system disorders
Hemoglobin	64/92 (69.6%)		65/87 (74.7%)
Gastrointestinal disorders
Constipation	34/92 (37%)		31/87 (35.6%)
Diarrhea	15/92 (16.3%)		14/87 (16.1%)
Distention/bloating, abdominal	5/92 (5.4%)		2/87 (2.3%)
Heartburn/dyspepsia	7/92 (7.6%)		4/87 (4.6%)
Mucositis/stomatitis (clinical exam) - Oral cavity	5/92 (5.4%)		5/87 (5.7%)
Mucositis/stomatitis (functional/symp) - Oral cav	6/92 (6.5%)		1/87 (1.1%)
Nausea	34/92 (37%)		33/87 (37.9%)
Pain - Abdomen NOS	13/92 (14.1%)		11/87 (12.6%)
Pain - Stomach	5/92 (5.4%)		0/87 (0%)
Vomiting	14/92 (15.2%)		17/87 (19.5%)
General disorders
Edema: limb	7/92 (7.6%)		9/87 (10.3%)
Fatigue (asthenia, lethargy, malaise)	65/92 (70.7%)		56/87 (64.4%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	7/92 (7.6%)		4/87 (4.6%)
Pain - Chest/thorax NOS	16/92 (17.4%)		12/87 (13.8%)
Pain-Other	3/92 (3.3%)		7/87 (8%)
Rigors/chills	8/92 (8.7%)		3/87 (3.4%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	12/92 (13%)		9/87 (10.3%)
AST, SGOT	14/92 (15.2%)		12/87 (13.8%)
Alkaline phosphatase	17/92 (18.5%)		14/87 (16.1%)
Creatinine	10/92 (10.9%)		13/87 (14.9%)
Leukocytes (total WBC)	52/92 (56.5%)		50/87 (57.5%)
Lymphopenia	16/92 (17.4%)		23/87 (26.4%)
Metabolic/Laboratory-Other	7/92 (7.6%)		7/87 (8%)
Neutrophils/granulocytes (ANC/AGC)	53/92 (57.6%)		42/87 (48.3%)
Platelets	70/92 (76.1%)		62/87 (71.3%)
Weight loss	23/92 (25%)		8/87 (9.2%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	22/92 (23.9%)		20/87 (23%)
Anorexia	35/92 (38%)		28/87 (32.2%)
Calcium, serum-high (hypercalcemia)	6/92 (6.5%)		0/87 (0%)
Calcium, serum-low (hypocalcemia)	16/92 (17.4%)		12/87 (13.8%)
Dehydration	9/92 (9.8%)		6/87 (6.9%)
Glucose, serum-high (hyperglycemia)	27/92 (29.3%)		39/87 (44.8%)
Magnesium, serum-low (hypomagnesemia)	19/92 (20.7%)		10/87 (11.5%)
Potassium, serum-low (hypokalemia)	14/92 (15.2%)		21/87 (24.1%)
Sodium, serum-low (hyponatremia)	26/92 (28.3%)		24/87 (27.6%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general	14/92 (15.2%)		7/87 (8%)
Pain - Back	17/92 (18.5%)		17/87 (19.5%)
Pain - Chest wall	5/92 (5.4%)		3/87 (3.4%)
Pain - Extremity-limb	2/92 (2.2%)		6/87 (6.9%)
Pain - Joint	5/92 (5.4%)		9/87 (10.3%)
Nervous system disorders
Dizziness	7/92 (7.6%)		16/87 (18.4%)
Neuropathy: sensory	8/92 (8.7%)		13/87 (14.9%)
Pain - Head/headache	18/92 (19.6%)		12/87 (13.8%)
Taste alteration (dysgeusia)	6/92 (6.5%)		5/87 (5.7%)
Psychiatric disorders
Confusion	5/92 (5.4%)		2/87 (2.3%)
Insomnia	16/92 (17.4%)		15/87 (17.2%)
Mood alteration - anxiety	8/92 (8.7%)		11/87 (12.6%)
Mood alteration - depression	6/92 (6.5%)		6/87 (6.9%)
Renal and urinary disorders
Proteinuria	8/92 (8.7%)		1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	26/92 (28.3%)		32/87 (36.8%)
Dyspnea (shortness of breath)	38/92 (41.3%)		31/87 (35.6%)
Hemorrhage, pulmonary/upper respiratory - Nose	10/92 (10.9%)		7/87 (8%)
Voice changes/dysarthria	16/92 (17.4%)		4/87 (4.6%)
Skin and subcutaneous tissue disorders
Hair loss/Alopecia (scalp or body)	12/92 (13%)		19/87 (21.8%)
Vascular disorders
Hypertension	23/92 (25%)		2/87 (2.3%)
Hypotension	4/92 (4.3%)		6/87 (6.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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