Clinical trial NCT00126581: Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
Official title: A Phase II Randomized Study of OSI-774 (Erlotinib) (NSC #718781) With or Without Carboplatin/Paclitaxel in Patients With Previously Untreated Adenocarcinoma of the Lung Who Never Smoked or Were Former Light Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Adenocarcinoma
Lung Adenosquamous Carcinoma
Malignant Pericardial Effusion
Malignant Pleural Effusion
Minimally Invasive Lung Adenocarcinoma
Stage IIIB Lung Non-Small Cell Cancer AJCC v7
Stage IV Lung Non-Small Cell Cancer AJCC v7
Keywords: A Phase II Randomized Study of OSI-774
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-08-04
Enrollment: 188
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 erlotinib hydrochloride with or without carboplatin and paclitaxel works in treating patients with stage III-IV non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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, by stopping them from dividing, or by stopping them from spreading. Giving erlotinib hydrochloride together with carboplatin and paclitaxel may kill more tumor cells than giving either drug alone.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the distribution of progression-free survival (PFS) in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) (erlotinib hydrochloride) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

SECONDARY OBJECTIVES:

I. To determine the radiographic response rate in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

II. To determine the frequency of epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutations and anaplastic lymphoma kinase (ALK) translocations in patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers.

III. To determine the response rate and time to progression in patients with and without EGFR mutations treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

IV. To determine the response rate and time to progression in patients with and without K-ras mutations treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

V. To determine the median and overall survival of patients with previously untreated advanced adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

VI. To estimate the response rate, progression-free, and overall survival of patients with echinoderm microtubule associated protein like (EML)4-ALK translocation who received OSI-774 erlotinib alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

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

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive erlotinib hydrochloride as in Arm I. Patients also receive paclitaxel intravenously (IV) over 1-3 hours and carboplatin IV over 15-30 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to receive erlotinib hydrochloride alone as above.

After completion of study treatment, patients are followed at least every 3 months for 1 year and then every 6 months for up to 2 years.

Eligibility criteria: Inclusion Criteria:

* Histologic documentation of primary lung adenocarcinoma including any variant thereof such as pure or mixed bronchioloalveolar carcinoma or adenosquamous cell carcinoma; patients with non-small cell lung cancer (NSCLC) not otherwise specified (NOS) are not eligible

  * Pathology block or unstained slides from initial or subsequent diagnosis must be available for sequencing of EGFR, K-ras, Erb-2 and B-raf; patients need to have had at least a core biopsy; patients whose diagnosis was made through a fine needle aspirate will not have sufficient material for mutational analysis and are not eligible
* Select stage IIIB with cytologically documented malignant pleural or pericardial effusion OR stage IV disease
* Patients must be chemotherapy naïve; they may not have received neo-adjuvant or adjuvant chemotherapy
* No prior exposure to OSI-774 (erlotinib) or other treatments targeting the human epidermal growth factor receptor (HER) family axis (e.g., trastuzumab, gefitinib, cetuximab, lapatinib, etc.)
* No uncontrolled central nervous system metastases (i.e., any known central nervous system \[CNS\] lesion which is radiographically unstable, symptomatic and/or requiring corticosteroids); patients must be \>= 3 weeks beyond completing cranial irradiation and off corticosteroid therapy
* \>= 3 weeks since prior radiation therapy
* \>= 3 weeks since prior major surgery
* No treatment with an investigational agent currently or within the last 28 days
* Non-smoker or former light smoker; non-smoker is defined as a person who smoked =\< 100 cigarettes in their lifetime while a former light smoker is a patient who smoked between \> 100 cigarettes AND =\< 10 pack years AND quit \>= 1 year ago; this must be documented on the On-study Form (C-1405)
* Eastern Cooperative Oncology Group (ECOG) 0 or 1
* Non-pregnant and non-nursing
* No dysphagia or active gastrointestinal disease or disorder that alters gastrointestinal motility or absorption; no lack of integrity of the gastrointestinal tract (e.g., a significant surgical resection of the stomach or small bowel); patients unable to swallow intact tablets must be able to swallow tablets dissolved in water
* Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan; lesions that are considered non-measurable include the following:

  * Bone lesions
  * Leptomeningeal disease
  * Ascites
  * Pleural/pericardial effusion
  * Lymphangitis cutis/pulmonis
  * Abdominal masses that are not confirmed and followed by imaging techniques
  * Cystic lesions
* Granulocyte \>= 1,500/mcl
* Platelet count \>= 100,000/mcl
* Hemoglobin \>= 9.0 g/dL
* Total bilirubin =\< upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 x ULN
* Creatinine =\< 1.5 mg/dl

Primary outcomes:
measure: 18 Weeks Progression Free Survival (PFS) Rate
timeFrame: At 18 weeks
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Duration of Study (up to 3 years)
measure: Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.
timeFrame: Duration of study (up to 3 years)
Other outcomes:
measure: Overall Survival
timeFrame: Time from randomization to death (up to 3 years)
measure: Progression Free Survival (PFS) by Epidermal Growth Factor Receptor (EGFR) Mutation Status
timeFrame: Duration of treatment (up to 3 years)
measure: Overall Response Rate by EGFR Mutation Status
timeFrame: Duration of study (up to 3 years)
measure: Progression Free Survival With KRAS Mutation Status
timeFrame: Duration of study (up to 3 years)
measure: Overall Response Rate With KRAS Mutational Status
timeFrame: Duration of study (up to 3 years)
Locations:
city: Castro Valley
country: United States
facility: East Bay Radiation Oncology Center
state: California
city: Castro Valley
country: United States
facility: Eden Hospital Medical Center
state: California
city: Castro Valley
country: United States
facility: Valley Medical Oncology Consultants-Castro Valley
state: California
city: Emeryville
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Fremont
country: United States
facility: Valley Medical Oncology Consultants-Fremont
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Oakland
country: United States
facility: Highland General Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Hematology and Oncology Associates-Oakland
state: California
city: Oakland
country: United States
facility: Tom K Lee Inc
state: California
city: Pleasanton
country: United States
facility: Valley Care Health System - Pleasanton
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-San Diego Mission
state: California
city: San Diego
country: United States
facility: Veterans Administration-San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Pablo
country: United States
facility: Doctors Medical Center- JC Robinson Regional Cancer Center
state: California
city: Middletown
country: United States
facility: Middlesex Hospital
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Jupiter
country: United States
facility: Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: La Grange
country: United States
facility: AMITA Health Adventist Medical Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Kokomo
country: United States
facility: Community Howard Regional Health
state: Indiana
city: La Porte
country: United States
facility: IU Health La Porte Hospital
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center-Mishawaka
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center/Weinberg Cancer Institute
state: Maryland
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Danvers
country: United States
facility: Mass General/North Shore Cancer Center
state: Massachusetts
city: Hyannis
country: United States
facility: Cape Cod Hospital
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: South Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Medical Center Saint Joseph
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Columbia
country: United States
facility: Veterans Administration
state: Missouri
city: Columbia
country: United States
facility: University of Missouri - Ellis Fischel
state: Missouri
city: Jefferson City
country: United States
facility: Capital Region Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Center for Cancer Care and Research
state: Missouri
city: Grand Island
country: United States
facility: CHI Health Saint Francis
state: Nebraska
city: North Platte
country: United States
facility: Great Plains Health Callahan Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Nashua
country: United States
facility: Saint Joseph Hospital
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York-East Syracuse
state: New York
city: Lake Success
country: United States
facility: Northwell Health NCORP
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Ralph Lauren Center for Cancer Care and Prevention
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: Saint Joseph's Hospital Health Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Hendersonville
country: United States
facility: Margaret R Pardee Memorial Hospital
state: North Carolina
city: Kinston
country: United States
facility: Vidant Oncology-Kinston
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Pawtucket
country: United States
facility: Memorial Hospital of Rhode Island
state: Rhode Island
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Roper Hospital
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: Greenville Memorial Hospital
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Eastside
state: South Carolina
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont and State Agricultural College
state: Vermont
city: Kilmarnock
country: United States
facility: Rappahannock General Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Alliance for Clinical Trials in Oncology
name: Pasi A Janne
role: PRINCIPAL_INVESTIGATOR
References: