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

Extensive Stage Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00828139
• Other study ID #: NCI-2009-01182
• Secondary ID: NCI-2009-01182SW
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 22, 2009
• Last updated: April 9, 2014
• Start date: May 2009

Study information

• Verified date: April 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 137
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Extensive Stage Small Cell Lung Cancer
• Lung Neoplasms
• Recurrent Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Biological:
• ziv-aflibercept
Given IV

Drug:
• topotecan hydrochloride
Given IV

Locations

Country	Name	City	State
United States	Akron General Medical Center	Akron	Ohio
United States	San Luis Valley Regional Medical Center	Alamosa	Colorado
United States	Saint Anthony's Health	Alton	Illinois
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan	Ann Arbor	Michigan
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	Randolph Hospital	Asheboro	North Carolina
United States	Atlanta Regional CCOP	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Well Star Cobb Hospital	Austell	Georgia
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Saint Francis Hospital and Health Centers	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana
United States	Montana Cancer Consortium CCOP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Columbus CCOP	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Carolinas Medical Center - Northeast	Concord	North Carolina
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Oakwood Hospital	Dearborn	Michigan
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Medical Center	Duarte	California
United States	The Shaw Regional Cancer Center	Edwards	Colorado
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Arnot Ogden Medical Center	Elmira	New York
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Gaston Memorial Hospital	Gastonia	North Carolina
United States	Adirondack Cancer Center	Glens Falls	New York
United States	Valley View Hospital Cancer Center	Glenwood Springs	Colorado
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Gulfport Memorial Hospital	Gulfport	Mississippi
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	Hays Medical Center	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	High Point Regional Hospital	High Point	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Methodist Hospital	Houston	Texas
United States	Saint Luke's Episcopal Hospital	Houston	Texas
United States	Veterans Administration Medical Center	Houston	Texas
United States	Promise Regional Medical Center-Hutchinson	Hutchinson	Kansas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	NEA Baptist Memorial Hospital	Jonesboro	Arkansas
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas City Cancer Center-West	Kansas City	Kansas
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	University of Tennessee - Knoxville	Knoxville	Tennessee
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Hospital	Lansing	Michigan
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	University of Kentucky	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Texas Tech University Health Sciences Center	Lubbock	Texas
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Memorial Hospital Of Martinsville	Martinsville	Virginia
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee - Memphis	Memphis	Tennessee
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	Holy Family Hospital	Methuen	Massachusetts
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Winthrop University Hospital	Mineola	New York
United States	Community Medical Hospital	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Providence Hospital	Mobile	Alabama
United States	Montrose Memorial Hospital	Montrose	Colorado
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	El Camino Hospital	Mountain View	California
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Interim LSU Public Hospital	New Orleans	Louisiana
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Licking Memorial Hospital	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Breast Surgeons Inc	Oakland	California
United States	Bay Area Tumor Institute CCOP	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Olathe Cancer Center	Olathe	Kansas
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Via Christi Hospital-Pittsburg	Pittsburg	Kansas
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Western Oncology Research Consortium	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Highland Hospital	Rochester	New York
United States	Interlakes Foundation Inc-Rochester	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	Highlands Oncology Group-Rogers	Rogers	Arkansas
United States	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California at Davis Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Salem Hospital	Salem	Oregon
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Southwest Oncology Group	San Antonio	Texas
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	The Polyclinic	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	United General Hospital	Sedro-Woolley	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Upstate Carolina CCOP	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Rockwood Clinic	Spokane	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas
United States	Stormont-Vail Regional Health Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Arizona Cancer Center at UMC Orange Grove	Tucson	Arizona
United States	Arizona Cancer Center at University Medical Center North	Tucson	Arizona
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	South Georgia Medical Center	Valdosta	Georgia
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita CCOP	Wichita	Kansas
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Wright-Patterson Medical Center	Wright-Patterson Afb	Ohio
United States	Metro Health Hospital	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis HealthCare System	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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, assessed up to 3 months	No
Secondary	Overall survival	Estimated to within at least 15% (95% confidence interval).	6 months	No
Secondary	Individual toxicity proportions as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0	Estimated to within at least 15% (95% confidence interval).	6 months	Yes
Secondary	Response rate (confirmed and unconfirmed, complete and partial responses)	Estimated to within at least 17% (95% confidence interval.	Up to 2 years	No