Carboplatin, Paclitaxel, and Bevacizumab With or Without Erlotinib Hydrochloride in Treating Non-Smokers With Advanced Non-Small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer Clinical Trial

Official title:

Randomized Double-Blind Placebo Controlled Phase II Trial Evaluating Erlotinib in Non-Smoking Patients With (Bevacizumab-Eligible and Ineligible) Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00976677
• Other study ID #: NCI-2011-01967
• Secondary ID: NCI-2011-01967EC
• Status: Terminated
• Phase: Phase 2
• First received: September 11, 2009
• Last updated: May 23, 2014
• Start date: January 2010
• Est. completion date: November 2013

Study information

• Verified date: December 2013
• 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 studies how well carboplatin, paclitaxel, and bevacizumab work with or without erlotinib hydrochloride in treating non-smokers with advanced non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving combination chemotherapy together with bevacizumab is more effective with or without erlotinib hydrochloride in treating patients with non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS) of non-smokers with advanced non-small cell lung cancer (NSCLC) randomized to standard of care (either carboplatin/paclitaxel with or without bevacizumab), or standard of care plus erlotinib hydrochloride.

SECONDARY OBJECTIVES:

I. To evaluate the overall survival from day of randomization. II. To evaluate response rate. III. To evaluate relative toxicity. IV. To determine the frequency of epidermal growth factor receptor (EGFR) and Kras mutations in non-smokers with NSCLC and correlate mutation status with response rate and progression free survival.

V. To obtain blood and tissue specimens for further marker-based exploratory analyses regarding EGFR inhibitors.

VI. To evaluate EGFR positivity by fluorescence in situ hybridization (FISH) as a predictor of improved PFS in patients treated with erlotinib hydrochloride.

OUTLINE: This is a multicenter study. Patients are stratified according to gender and eligibility for bevacizumab therapy (ineligible vs eligible and willing to receive bevacizumab vs eligible and not willing to receive bevacizumab). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes (with or without bevacizumab IV over 30-90 minutes) on day 1. Patients also receive placebo orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive placebo (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive paclitaxel and carboplatin (with or without bevacizumab) as in arm I. Patients also receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable or responding disease may continue to receive erlotinib hydrochloride (with or without bevacizumab) as above in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected for correlative laboratory studies.

After completion of study treatment, patients are followed up periodically for 5 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: November 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Measurable disease as defined by Response Criteria In Solid Tumors (RECIST) criteria

• Baseline measurements and evaluations of all sites of disease must be obtained =< 4 weeks (28 days) prior to randomization

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

• No prior chemotherapy for lung cancer; prior chemotherapy for an unrelated condition is allowed if completed > 3 years prior to date of randomization

• Histological or cytologic evidence of non-small cell lung cancer

• Patients must not have any additional active, invasive malignancies requiring therapy

• Patients must have smoked less than or equal to 100 cigarettes in their lifetime

• Stage IV or IIIB (with pleural or pericardial effusion or multifocal pleural involvement) or recurrence after prior curative resection or definitive radiation

• Prior radiation therapy (RT) is allowed, provided RT has ended at least 2 weeks (14 days) prior to date of randomization; patients must have recovered from any adverse events related to the RT (except alopecia and grade 1 neuropathy); no previous irradiation to the only site of measurable disease, unless that site has had subsequent evidence of pathologic or radiologic progression

• Absolute neutrophil count (ANC) >= 1500/mm^3

• Platelet count >= 100,000/mm^3

• Bilirubin =< 1.5 mg/dl

• Creatinine =< 2.0 mg/dl

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) =< 3 X institutional upper limit of normal (ULN)

• Women must not be pregnant or breast-feeding due to unknown interaction between erlotinib and the developing fetus or newborns potentially exposed to erlotinib by ingestion of lactated milk; all females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy

• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception

• Patients must not have clinically significant ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patient must meet the following criteria:

• Non-squamous histology

• No antecedent hemoptysis

• International normalized ratio (INR) =< 3 within 4 weeks (28 days) prior to randomization

• Patients may be on a stable regimen of therapeutic anticoagulation or may be receiving prophylactic anticoagulation of venous access devices, provided that coagulation studies met entry criteria; caution must be exercised for patients requiring anticoagulation, including treatment with low dose heparin or low molecular weight heparin for deep vein thrombosis (DVT) prophylaxis while on study due to an increased risk of bleeding with bevacizumab

• No history of untreated brain metastases NOTE: Recent data (PASSPORT, ATLAS, AIRES) suggest that bevacizumab can be given in patients with treated brain metastases; investigators can use their discretion in deciding whether to use bevacizumab in patients who fulfill these criteria

• Urine dipstick must be =< 0-1+ within 4 weeks (28 days) of randomization. If urine dipstick is > 1+ then the Urine Protein Creatinine (UPC) ratio must be calculated

• Patients must have no history of thrombotic or hemorrhagic disorders

• Patients with history of hypertension must be well-controlled (blood pressure [BP] =< 150/90 within 4 weeks [28 days] of randomization) and on a stable regimen of anti-hypertensive therapy (within 4 weeks of randomization)

• Patients must not have serious non-healing wound ulcer, bone fracture, or major surgical procedure within 28 days prior to randomization

• Patients with a known history of myocardial infarction or other evidence of arterial thrombotic disease (angina) will be allowed on study only if they have had no evidence of active disease for at least 6 months prior to randomization

• Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to randomization

• Patients must not have significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization

• Patients must not have clinically significant cardiovascular disease including:

• History of cerebral vascular accident (CVA) within 6 months

• New York Heart Association grade II or greater congestive heart failure

• Serious and inadequately controlled cardiac arrhythmia

• Clinically significant peripheral vascular disease (symptomatic with intermittent claudications or < 6 months from a bypass operation)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-small Cell Lung Cancer
• Stage IIIB Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Intervention

Drug:
• erlotinib hydrochloride
Given PO
• paclitaxel
Given IV
• carboplatin
Given IV

Biological:
• bevacizumab
Given IV

Locations

Country	Name	City	State
United States	McFarland Clinic	Ames	Iowa
United States	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Aultman Health Foundation	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Mercy Medical Center	Canton	Ohio
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Association	Cedar Rapids	Iowa
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Case Western Reserve University	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Parkland Memorial Hospital	Dallas	Texas
United States	Saint Paul Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Zale Lipshy University Hospital	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Oakwood Hospital	Dearborn	Michigan
United States	Colorado Cancer Research Program CCOP	Denver	Colorado
United States	Exempla Saint Joseph Hospital	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	Saint Anthony Central Hospital	Denver	Colorado
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazelton	Hazleton	Pennsylvania
United States	Allegiance Health	Jackson	Michigan
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Sparrow Hospital	Lansing	Michigan
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	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio
United States	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois
United States	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois
United States	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois
United States	Spector, David MD (UIA Investigator)	Moline	Illinois
United States	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois
United States	Trinity Medical Center	Moline	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Saint Joseph Mercy Port Huron	Port Huron	Michigan
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Geisinger Medical Group	State College	Pennsylvania
United States	North Suburban Medical Center	Thornton	Colorado
United States	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania
United States	Lankenau Hospital	Wynnewood	Pennsylvania
United States	Mainline Health CCOP	Wynnewood	Pennsylvania

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)	Progression-free survival (PFS) is defined to be the time from randomization to progression of disease or death, whichever occurs first. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	Every 6 weeks during treatment and every 3 months in follow-up until disease progression or up to 5 years	No