Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer

Stage IV Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-squamous, Non-small Cell Lung Cancer

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
• 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
• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Bronchiolo-Alveolar
• Bronchioloalveolar Lung Carcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Large Cell Lung Carcinoma
• Lung Adenocarcinoma
• Lung Neoplasms
• Recurrent Non-Small Cell Lung Carcinoma
• Stage IV Non-Small Cell Lung Cancer

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