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

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)

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.

Study Overview

• Status: Completed
• Conditions: Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer
• Intervention / Treatment: Drug: topotecan hydrochloride; Biological: ziv-aflibercept

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

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

II. 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 Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36202
      • Northeast Alabama Regional Medical Center
    • Mobile, Alabama, United States, 36608
      • Providence Hospital
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Cancer Center at UMC Orange Grove
    • Tucson, Arizona, United States, 85719
      • Arizona Cancer Center at University Medical Center North
    • Tucson, Arizona, United States, 85724
      • University of Arizona Health Sciences Center
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Memorial Hospital
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group-Rogers
  • California
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants-Castro Valley
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute CCOP
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Bay Area Breast Surgeons Inc
    • Oakland, California, United States, 94609
      • Larry G Strieff MD Medical Corporation
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Sacramento, California, United States, 95817
      • University of California at Davis Cancer Center
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
  • Colorado
    • Alamosa, Colorado, United States, 81101
      • San Luis Valley Regional Medical Center
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Edwards, Colorado, United States, 81632
      • The Shaw Regional Cancer Center
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital Cancer Center
    • Grand Junction, Colorado, United States, 81502
      • Saint Mary's Hospital and Regional Medical Center
    • Montrose, Colorado, United States, 81401
      • Montrose Memorial Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis Hospital and Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Atlanta, Georgia, United States, 30342
      • Saint Joseph's Hospital of Atlanta
    • Atlanta, Georgia, United States, 30342
      • Atlanta Regional CCOP
    • Austell, Georgia, United States, 30106
      • Well Star Cobb Hospital
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Fayetteville, Georgia, United States, 30214
      • Piedmont Fayette Hospital
    • Lawrenceville, Georgia, United States, 30045
      • Gwinnett Medical Center
    • Marietta, Georgia, United States, 30060
      • WellStar Kennestone Hospital
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
    • Rome, Georgia, United States, 30165
      • Harbin Clinic Medical Oncology and Clinical Research
    • Savannah, Georgia, United States, 31403
      • Memorial Health University Medical Center
    • Valdosta, Georgia, United States, 31603
      • South Georgia Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Center of Decatur
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Saint Francis Hospital and Health Centers
    • Richmond, Indiana, United States, 47374
      • Reid Hospital and Health Care Services
  • Iowa
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center - East Campus
    • Davenport, Iowa, United States, 52804
      • Genesis Medical Center - West Campus
  • Kansas
    • Anthony, Kansas, United States, 67003
      • Hospital District Sixth of Harper County
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Hays, Kansas, United States, 67601
      • Hays Medical Center
    • Hutchinson, Kansas, United States, 65702
      • Promise Regional Medical Center-Hutchinson
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Kansas City, Kansas, United States, 66112
      • Kansas City Cancer Center-West
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Cancer Center of Kansas-Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Olathe, Kansas, United States, 66061
      • Olathe Cancer Center
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pittsburg, Kansas, United States, 66762
      • Via Christi Hospital-Pittsburg
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Topeka, Kansas, United States, 66606
      • Saint Francis Hospital and Medical Center - Topeka
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Regional Health Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Wichita CCOP
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
    • New Orleans, Louisiana, United States, 70112
      • Interim LSU Public Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Methuen, Massachusetts, United States, 01844
      • Holy Family Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Pontiac, Michigan, United States, 48341-2985
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Mississippi
    • Gulfport, Mississippi, United States, 39502
      • Gulfport Memorial Hospital
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Kansas City, Missouri, United States, 64128
      • Kansas City Veterans Affairs Medical Center
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Hospital
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis-Cape Girardeau CCOP
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Springfield, Missouri, United States, 65802
      • Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies PC
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Great Falls, Montana, United States, 59405
      • Big Sky Oncology
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
  • New York
    • Elmira, New York, United States, 14905
      • Arnot Ogden Medical Center
    • Glens Falls, New York, United States, 12801
      • Adirondack Cancer Center
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Rochester, New York, United States, 14623
      • Interlakes Foundation Inc-Rochester
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Concord, North Carolina, United States, 28025
      • Carolinas Medical Center - Northeast
    • Gastonia, North Carolina, United States, 28054
      • Gaston Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Greensboro, North Carolina, United States, 27403
      • Cone Health Cancer Center
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • High Point, North Carolina, United States, 27261
      • High Point Regional Hospital
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Memorial Hospital
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • Ohio
    • Akron, Ohio, United States, 44307
      • Akron General Medical Center
    • Bellefontaine, Ohio, United States, 43311
      • Mary Rutan Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Columbus, Ohio, United States, 43215
      • Columbus CCOP
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97213
      • Western Oncology Research Consortium
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
    • Salem, Oregon, United States, 97301
      • Salem Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Hospital
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • Upstate Carolina CCOP
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee - Memphis
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch at Galveston
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Methodist Hospital
    • Houston, Texas, United States, 77030
      • Saint Luke's Episcopal Hospital
    • Houston, Texas, United States, 77030
      • Veterans Administration Medical Center
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center
    • San Antonio, Texas, United States, 78245
      • Southwest Oncology Group
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Martinsville, Virginia, United States, 24115
      • Memorial Hospital Of Martinsville
  • Washington
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology PLLC
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Sedro-Woolley, Washington, United States, 98284
      • United General Hospital
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99220
      • Rockwood Clinic
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Vancouver, Washington, United States, 98684
      • Compass Oncology Vancouver
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Drug: topotecan hydrochloride; Given IV; Other Names: Hycamtin; SKF S-104864-A; hycamptamine; TOPO; Biological: ziv-aflibercept; Given IV; Other Names: aflibercept; vascular endothelial growth factor trap; VEGF Trap; Zaltrap
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: Hycamtin; SKF S-104864-A; hycamptamine; TOPO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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.	Disease assessments were performed every 6 weeks, up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Estimated to within at least 15% (95% confidence interval).	Weekly, up to 2 years.
Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses)	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.	Disease assessment for response were performed every 6 weeks, up to 2 years.
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs	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.	Toxicity assessment was evaluated after each cycle (21 days), up to 2 years.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Allen, Southwest Oncology Group

Publications and helpful links

General Publications

• Lara PN Jr, Moon J, Redman MW, Semrad TJ, Kelly K, Allen JW, Gitlitz BJ, Mack PC, Gandara DR. Relevance of platinum-sensitivity status in relapsed/refractory extensive-stage small-cell lung cancer in the modern era: a patient-level analysis of southwest oncology group trials. J Thorac Oncol. 2015 Jan;10(1):110-5. doi: 10.1097/JTO.0000000000000385.
• Allen JW, Moon J, Redman M, Gadgeel SM, Kelly K, Mack PC, Saba HM, Mohamed MK, Jahanzeb M, Gandara DR. Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer. J Clin Oncol. 2014 Aug 10;32(23):2463-70. doi: 10.1200/JCO.2013.51.4109. Epub 2014 Jul 7.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 22, 2009
• First Submitted That Met QC Criteria: January 22, 2009
• First Posted (Estimate): January 23, 2009

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: July 21, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Topotecan; Aflibercept; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-01182 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SWOG-S0802; CDR0000632614; S0802 (Other Identifier: CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No