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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00955305
Other study ID # NCI-2011-01960
Secondary ID NCI-2011-01960E3
Status Terminated
Phase Phase 2
First received
Last updated
Start date March 2010
Est. completion date November 2016

Study information

Verified date May 2018
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This randomized phase II trial studies how well carboplatin, paclitaxel, and bevacizumab (CPB) work when given with or without cixutumumab in treating patients with non-small cell lung cancer that is stage IV or has come back (recurrent). Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Other types of monoclonal antibodies, such as cixutumumab, may find tumor cells and help kill them. It is not yet known whether giving more than one drug (combination chemotherapy) together with bevacizumab is more effective when given with or without cixutumumab in treating patients with non-small cell lung cancer.


Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival with the combination of carboplatin, paclitaxel, and bevacizumab, and +/- IMC-A12 (cixutumumab) in patients with advanced, non-squamous, non-small cell lung cancer.

SECONDARY OBJECTIVES:

I. To evaluate overall survival and response rate of the above combination in patients with non-squamous, advanced non-small cell lung cancer.

II. To evaluate the toxicities of the above combination in patients with non-squamous advanced non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A (CPB): Patients receive carboplatin intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and bevacizumab IV over 30-90 minutes on day 1.

ARM B (CPB+cixutumumab): Patients receive carboplatin, paclitaxel, and bevacizumab as in Arm A. Patients also receive cixutumumab (IMC-A12) IV over 1 hour on days 1, 8, and 15.

In both arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.


Recruitment information / eligibility

Status Terminated
Enrollment 175
Est. completion date November 2016
Est. primary completion date January 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Histologically or cytologically confirmed with non-squamous, non-small cell lung cancer (NSCLC)

- Advanced NSCLC defined as either recurrent disease after prior radiation or surgery or stage IV (M1a or M1b) based on the TNM staging system (American Joint Committee on Cancer [AJCC] 2009)

- Measurable disease as defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). All sites of disease (of target and non-target disease sites) must be obtained within 4 weeks prior to randomization

- A head computed tomography (CT) or magnetic resonance imaging (MRI) required within 4 weeks prior to randomization

- Prior radiation therapy (RT) is allowed if it has been completed 3 weeks prior to randomization and patient has recovered from any adverse events related to RT

- Brain metastases are allowed, provided they have been treated with surgery and/or radiotherapy, the patient is neurologically stable, and repeat brain imaging shows no progression in the brain; at least 6 weeks should have elapsed from the time of craniotomy and at least 4 weeks from radiotherapy

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Absolute neutrophil count (ANC) = 1500/mm³

- Platelet count = 100,000/mm³

- Total bilirubin within institutional upper limit of normal (ULN)

- Serum creatinine = 1.5 x ULN

- Fasting blood glucose within normal range (fasting < 120 mg/dL or below ULN)

- Alkaline phosphatase (ALP) = 3 x ULN

- Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 x ULN

- Urine dipstick must be = 0-1+ within 2 weeks (14 days) of randomization; if urine dipstick result is > 1+, a calculation of urine protein creatinine (UPC) ratio is required; patients must have a UPC ratio < 1.0 to participate in the study

- Neuropathy, if present at baseline, must be = Common Terminology Criteria for Adverse Events (CTCAE) grade 1

- Patients with a history of hypertension must be well-controlled (= 150/90) on a stable regimen of anti-hypertensive therapy

- Women of childbearing potential and sexually active males should use an accepted and effective method of contraception while on treatment and for 3 months thereafter

Exclusion Criteria:

- Prior chemotherapy or biologic/molecular targeted therapy for advanced NSCLC. Prior chemotherapy and/or biological/molecular targeted therapy as part of initial potentially curative therapy (one regimen of induction and/or adjuvant and/or concurrent chemoradiotherapy) was allowed provided it had been completed 1 year or more prior to randomization

- Prior treatment with IMC-A12 or another insulin-like growth factor 1 receptor (IGF-1R) inhibitor

- Patients on therapeutic anticoagulation; patient's international normalized ratio (INR) must be = 1.5 or partial thromboplastin time (PTT) = upper limits of normal within 2 weeks prior to randomization to be eligible; prophylactic anticoagulation of venous access devices is allowed provided the above criteria have been met

- Prior allergic reaction to compounds of chemical or biologic composition similar to those of IMC-A12

- Hypersensitivity to any component of bevacizumab

- Poorly controlled diabetes mellitus

- History of other invasive malignancies unless there is no active disease and all treatment has been completed = 3 years prior to randomization; patients with history of in-situ malignancies and curatively resected nonmelanomatous skin cancer are eligible

- History of thrombotic or hemorrhagic disorders

- History of bleeding diathesis or coagulopathy

- = grade 2 bleeding or any bleeding requiring intervention within 4 weeks prior to randomization

- History of gross hemoptysis (defined as = 1/2 teaspoon of bright red blood)

- Any of the following within 6 months prior to randomization:

- Abdominal fistula

- Gastrointestinal perforation

- Intra-abdominal abscess

- Previous myocardial infarction

- History of any central nervous system (CNS) cerebrovascular ischemia

- New York Heart Association (NYHA) > class II congestive heart failure or severe heart failure

- Unstable or symptomatic angina pectoris

- History of stroke

- Significant vascular disease

- Symptomatic peripheral vascular disease

- Ongoing, serious cardiac arrhythmia requiring medication at time of randomization

- Ongoing, active infection or ongoing fever at the time of randomization or any co-existing medical condition, psychiatric illness or limitations that would interfere with compliance of study requirements

- History of hypertensive crisis or hypertensive encephalopathy

- Any of the following within 4 weeks prior to randomization: a serious non-healing wound, ulcer, bone fracture, or major surgical procedure

- Anticipated major surgical procedure(s) during the course of the study

- Receiving daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function for chronic conditions; patients must not be receiving treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal); if patient was receiving any of the following: aspirin (> 325 mg/day), NSAID, and/or anti-platelet drugs, patient must have discontinued its use = 1 week prior to randomization

- Pregnant or breast-feeding

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Bevacizumab
Given IV
Drug:
Carboplatin
Given IV
Biological:
Cixutumumab
Given IV
Drug:
Paclitaxel
Given IV

Locations

Country Name City State
United States Summa Akron City Hospital/Cooper Cancer Center Akron Ohio
United States McFarland Clinic PC-William R Bliss Cancer Center Ames Iowa
United States Michigan Cancer Research Consortium CCOP Ann Arbor Michigan
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Fox Valley Hematology and Oncology Appleton Wisconsin
United States The Medical Center of Aurora Aurora Colorado
United States Mary Rutan Hospital Bellefontaine Ohio
United States Sanford Clinic North-Bemidgi Bemidji Minnesota
United States Saint Alphonsus Cancer Care Center-Boise Boise Idaho
United States Tufts Medical Center Boston Massachusetts
United States Boulder Community Hospital Boulder Colorado
United States Essentia Health Saint Joseph's Medical Center Brainerd Minnesota
United States Bryn Mawr Hospital Bryn Mawr Pennsylvania
United States Fairview Ridges Hospital Burnsville Minnesota
United States Mercy Medical Center Canton Ohio
United States Mercy Hospital Cedar Rapids Iowa
United States Oncology Associates at Mercy Medical Center Cedar Rapids Iowa
United States Cancer Center of Kansas - Chanute Chanute Kansas
United States West Virginia University Charleston Charleston West Virginia
United States Saint Joseph Hospital Chicago Illinois
United States Adena Regional Medical Center Chillicothe Ohio
United States The Christ Hospital Cincinnati Ohio
United States Case Western Reserve University Cleveland Ohio
United States Medical Oncology and Hematology Associates-West Des Moines Clive Iowa
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Columbus NCI Community Oncology Research Program Columbus Ohio
United States Doctors Hospital Columbus Ohio
United States Grant Medical Center Columbus Ohio
United States Mount Carmel Health Center West Columbus Ohio
United States Riverside Methodist Hospital Columbus Ohio
United States Mercy Hospital Coon Rapids Minnesota
United States Dallas VA Medical Center Dallas Texas
United States Parkland Memorial Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Geisinger Medical Center Danville Pennsylvania
United States Oakwood Hospital and Medical Center Dearborn Michigan
United States Grady Memorial Hospital Delaware Ohio
United States Colorado Cancer Research Program NCORP Denver Colorado
United States Porter Adventist Hospital Denver Colorado
United States Presbyterian - Saint Lukes Medical Center - Health One Denver Colorado
United States Rose Medical Center Denver Colorado
United States SCL Health Saint Joseph Hospital Denver Colorado
United States Iowa Lutheran Hospital Des Moines Iowa
United States Iowa Methodist Medical Center Des Moines Iowa
United States Iowa-Wide Oncology Research Coalition NCORP Des Moines Iowa
United States Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa
United States Medical Oncology and Hematology Associates-Laurel Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Saint John Hospital and Medical Center Detroit Michigan
United States Cancer Center of Kansas - Dodge City Dodge City Kansas
United States Essentia Health Cancer Center Duluth Minnesota
United States Essentia Health Saint Mary's Medical Center Duluth Minnesota
United States Miller-Dwan Hospital Duluth Minnesota
United States Veterans Adminstration New Jersey Health Care System East Orange New Jersey
United States Marshfield Clinic Cancer Center at Sacred Heart Eau Claire Wisconsin
United States Fairview-Southdale Hospital Edina Minnesota
United States Cancer Center of Kansas - El Dorado El Dorado Kansas
United States Swedish Medical Center Englewood Colorado
United States Roger Maris Cancer Center Fargo North Dakota
United States Sanford Clinic North-Fargo Fargo North Dakota
United States Sanford Medical Center-Fargo Fargo North Dakota
United States Hunterdon Medical Center Flemington New Jersey
United States Genesys Hurley Cancer Institute Flint Michigan
United States Genesys Regional Medical Center-West Flint Campus Flint Michigan
United States Hurley Medical Center Flint Michigan
United States Cancer Center of Kansas - Fort Scott Fort Scott Kansas
United States Unity Hospital Fridley Minnesota
United States Saint Mary's Hospital and Regional Medical Center Grand Junction Colorado
United States North Colorado Medical Center Greeley Colorado
United States PinnacleHealth Cancer Center-Community Campus Harrisburg Pennsylvania
United States Smilow Cancer Hospital Care Center at Saint Francis Hartford Connecticut
United States Ingalls Memorial Hospital Harvey Illinois
United States Geisinger Medical Center-Cancer Center Hazleton Hazleton Pennsylvania
United States Hinsdale Hematology Oncology Associates Incorporated Hinsdale Illinois
United States Hutchinson Area Health Care Hutchinson Minnesota
United States Cancer Center of Kansas-Independence Independence Kansas
United States Allegiance Health Jackson Michigan
United States Borgess Medical Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Cancer Center of Kansas-Kingman Kingman Kansas
United States Lakeland Regional Cancer Center Lakeland Florida
United States Saint Anthony Hospital Lakewood Colorado
United States Fairfield Medical Center Lancaster Ohio
United States Saint Mary Medical and Regional Cancer Center Langhorne Pennsylvania
United States Sparrow Hospital Lansing Michigan
United States Lawrence Memorial Hospital Lawrence Kansas
United States Cancer Center of Kansas-Liberal Liberal Kansas
United States Saint Rita's Medical Center Lima Ohio
United States Littleton Adventist Hospital Littleton Colorado
United States Saint Mary Mercy Hospital Livonia Michigan
United States Sky Ridge Medical Center Lone Tree Colorado
United States Longmont United Hospital Longmont Colorado
United States McKee Medical Center Loveland Colorado
United States Dean Hematology and Oncology Clinic Madison Wisconsin
United States Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota
United States Saint John's Hospital - Healtheast Maplewood Minnesota
United States Marietta Memorial Hospital Marietta Ohio
United States Cancer Center of Kansas - McPherson McPherson Kansas
United States Froedtert and the Medical College of Wisconsin Milwaukee Wisconsin
United States Abbott-Northwestern Hospital Minneapolis Minnesota
United States Hennepin County Medical Center Minneapolis Minnesota
United States Knox Community Hospital Mount Vernon Ohio
United States The Hospital of Central Connecticut New Britain Connecticut
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States New Ulm Medical Center New Ulm Minnesota
United States Licking Memorial Hospital Newark Ohio
United States Rutgers New Jersey Medical School Newark New Jersey
United States Cancer Center of Kansas - Newton Newton Kansas
United States Eastern Connecticut Hematology and Oncology Associates Norwich Connecticut
United States Oconomowoc Memorial Hospital-ProHealth Care Inc Oconomowoc Wisconsin
United States Alegent Health Lakeside Hospital Omaha Nebraska
United States Ottumwa Regional Health Center Ottumwa Iowa
United States Paoli Memorial Hospital Paoli Pennsylvania
United States Cancer Center of Kansas - Parsons Parsons Kansas
United States Albert Einstein Medical Center Philadelphia Pennsylvania
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Saint Joseph Mercy Port Huron Port Huron Michigan
United States Southern Ohio Medical Center Portsmouth Ohio
United States Pottstown Memorial Medical Center Pottstown Pennsylvania
United States Cancer Center of Kansas - Pratt Pratt Kansas
United States Saint Mary Corwin Medical Center Pueblo Colorado
United States North Memorial Medical Health Center Robbinsdale Minnesota
United States Swedish American Hospital Rockford Illinois
United States SwedishAmerican Regional Cancer Center/ACT Rockford Illinois
United States Saint Mary's of Michigan Saginaw Michigan
United States Metro Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota
United States Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota
United States Regions Hospital Saint Paul Minnesota
United States United Hospital Saint Paul Minnesota
United States Cancer Center of Kansas - Salina Salina Kansas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia
United States Saint Francis Regional Medical Center Shakopee Minnesota
United States Mercy Medical Center-Sioux City Sioux City Iowa
United States Saint Luke's Regional Medical Center Sioux City Iowa
United States Siouxland Regional Cancer Center Sioux City Iowa
United States Avera Cancer Institute Sioux Falls South Dakota
United States Avera McKennan Hospital and University Health Center Sioux Falls South Dakota
United States Springfield Regional Medical Center Springfield Ohio
United States Geisinger Medical Group State College Pennsylvania
United States Lakeview Hospital Stillwater Minnesota
United States North Suburban Medical Center Thornton Colorado
United States Charlotte Hungerford Hospital Center for Cancer Care Torrington Connecticut
United States Ridgeview Medical Center Waconia Minnesota
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States Waukesha Memorial Hospital Waukesha Wisconsin
United States Cancer Center of Kansas - Wellington Wellington Kansas
United States Reading Hospital West Reading Pennsylvania
United States SCL Health Lutheran Medical Center Wheat Ridge Colorado
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 NCI Community Oncology Research Program Wichita Kansas
United States Geisinger Wyoming Valley/Henry Cancer Center Wilkes-Barre Pennsylvania
United States Rice Memorial Hospital Willmar Minnesota
United States Cancer Center of Kansas - Winfield Winfield Kansas
United States Minnesota Oncology and Hematology PA-Woodbury Woodbury Minnesota
United States Lankenau Medical Center Wynnewood Pennsylvania
United States Main Line Health NCORP Wynnewood Pennsylvania
United States Genesis Healthcare System Cancer Care Center Zanesville Ohio

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Argiris, A., Lee, J., Leach, J.W., Schiller, J.H.: Safety analysis of a phase II randomized trial of carboplatin (C), Paclitaxel (P), bevacizumab (B) with or without cixutumumab (CX) in patients (pts) with advanced non-squamous, non-small cell lung cancer

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free Survival (PFS) Progression-free survival was defined as the time from randomization to progression or death without documentation of progression. For cases without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurs within 3 months following the date last known progression-free, in which case the death was counted as a failure.
Progression was evaluated using RECIST 1.1 criteria and defined as:
At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm.
OR
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years
Secondary Overall Survival (OS) Overall survival is defined as the time from randomization to death or date last known alive. Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years
Secondary Proportion of Patients With Objective Response Objective response was evaluated using the RECIST 1.1 criteria.
Objective response includes complete response (CR) and partial response (PR). Objective response is defined as disappearance of all target lesions or at least a 30% decrease in the sum of the diameters of target lesions. In addition, non-target lesions do not meet the criteria for disease progression and no new lesions were observed.
Assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry; up to 5 years
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