Clinical trial NCT00976677: Carboplatin, Paclitaxel, and Bevacizumab With or Without Erlotinib Hydrochloride in Treating Non-Smokers With Advanced Non-Small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-09-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Every 6 weeks during treatment and every 3 months in follow-up until disease progression or up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: The Medical Center of Aurora
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Denver
country: United States
facility: Saint Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Exempla Saint Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: Colorado Cancer Research Program CCOP
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: Saint Mary's Hospital and Regional Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Hartford
country: United States
facility: Saint Francis Hospital and Medical Center
state: Connecticut
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare Galesburg
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare-Havana
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Garneau, Stewart C MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Porubcin, Michael MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Sharis, Christine M MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Spector, David MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Stoffel, Thomas J MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare-Monmouth
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare-Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association CCOP
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Illinois CancerCare-Spring Valley
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Bettendorf
country: United States
facility: Constantinou, Costas L MD (UIA Investigator)
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Association
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium Community Clinical Oncology Program
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center-West Flint Campus
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Duluth
country: United States
facility: Essentia Health Duluth Clinic CCOP
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Saint Mary's Medical Center
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Hospital
state: Minnesota
city: Mount Holly
country: United States
facility: Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Voorhees
country: United States
facility: Virtua West Jersey Hospital Voorhees
state: New Jersey
city: Canton
country: United States
facility: Mercy Medical Center
state: Ohio
city: Canton
country: United States
facility: Aultman Health Foundation
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Mentor
country: United States
facility: Lake University Ireland Cancer Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Southwest General Health Center Ireland Cancer Center
state: Ohio
city: Orange Village
country: United States
facility: UHHS-Chagrin Highlands Medical Center
state: Ohio
city: Westlake
country: United States
facility: UHHS-Westlake Medical Center
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Medical Center-Cancer Center Hazelton
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of The University of Pennsylvania
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Mainline Health CCOP
state: Pennsylvania
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: Zale Lipshy University Hospital
state: Texas
city: Dallas
country: United States
facility: Saint Paul Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Madison
country: United States
facility: Dean Hematology and Oncology Clinic
state: Wisconsin
Study officials:
affiliation: Eastern Cooperative Oncology Group
name: Corey Langer
role: PRINCIPAL_INVESTIGATOR
References: