Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

Lung Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00126581
• Other study ID #: NCI-2009-00464
• Secondary ID: NCI-2009-00464CD
• Status: Completed
• Phase: Phase 2
• Start date: August 15, 2005
• Est. completion date: November 28, 2017

Study information

• Verified date: July 2019
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: November 28, 2017
• Est. primary completion date: June 30, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Adenocarcinoma, Bronchiolo-Alveolar
• Carcinoma, Adenosquamous
• Lung Adenocarcinoma
• Lung Adenosquamous Carcinoma
• Malignant Pericardial Effusion
• Malignant Pleural Effusion
• Minimally Invasive Lung Adenocarcinoma
• Pericardial Effusion
• Pleural Effusion
• Pleural Effusion, Malignant
• Stage IIIB Lung Non-Small Cell Cancer AJCC v7
• Stage IV Lung Non-Small Cell Cancer AJCC v7

Intervention

Drug:
• Carboplatin
Given IV
• Erlotinib
Given PO
• Erlotinib Hydrochloride
Given PO
• Paclitaxel
Given IV

Locations

Country	Name	City	State
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Missouri Cancer Associates	Columbia	Missouri
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Veterans Administration	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mass General/North Shore Cancer Center	Danvers	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Saint Rose Hospital	Hayward	California
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Capital Region Medical Center	Jefferson City	Missouri
United States	Jupiter Medical Center	Jupiter	Florida
United States	Rappahannock General Hospital	Kilmarnock	Virginia
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Community Howard Regional Health	Kokomo	Indiana
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	Northwell Health NCORP	Lake Success	New York
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Lowell General Hospital	Lowell	Massachusetts
United States	North Shore University Hospital	Manhasset	New York
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Middlesex Hospital	Middletown	Connecticut
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	El Camino Hospital	Mountain View	California
United States	Saint Joseph Hospital	Nashua	New Hampshire
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Ralph Lauren Center for Cancer Care and Prevention	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Cancer Care Associates	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Valley Care Health System - Pleasanton	Pleasanton	California
United States	Valley Medical Oncology Consultants	Pleasanton	California
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	University of California San Diego	San Diego	California
United States	Veterans Administration-San Diego Medical Center	San Diego	California
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Shore Hospital	South Weymouth	Massachusetts
United States	Saint Joseph's Hospital Health Center	Syracuse	New York
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Wilson Medical Center	Wilson	North Carolina

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
Other	Overall Survival	Overall survival (OS) is defined as the time from patient randomization (arm assignment) to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.	Time from randomization to death (up to 3 years)
Other	Progression Free Survival (PFS) by Epidermal Growth Factor Receptor (EGFR) Mutation Status	PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.; EGFR mutations were performed at the Dana-Farber Cancer Institute using a sensitive heteroduplex method coupled with enzymatic digestion as previously reported (Janne PA, et al: A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin Cancer Res 12:751-758, 2006). All positive findings were independently verified and subjected to sequencing. The mutation analyses were blinded to the participants' clinical outcome.	Duration of treatment (up to 3 years)
Other	Overall Response Rate by EGFR Mutation Status	Response and EGFR mutation status are defined in previous outcome measures.	Duration of study (up to 3 years)
Other	Progression Free Survival With KRAS Mutation Status	Progression free survival is defined in previous outcome measures. GIven the small number of KRAS mutant participants, the analysis combines data from both arms.	Duration of study (up to 3 years)
Other	Overall Response Rate With KRAS Mutational Status	Overall response is defined in previous outcome measures. GIven the small number of KRAS mutant participants in each treatment arm, the analysis combines data from both arms.	Duration of study (up to 3 years)
Primary	18 Weeks Progression Free Survival (PFS) Rate	The product limit estimator developed by Kaplan Meier will be used to graphically describe progression free survival for patients randomized to each study arm.; The 18 week progression-free survival rate was defined as the proportion of patients that were alive progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.	At 18 weeks
Secondary	Overall Response Rate	The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. An exact binomial confidence interval will be computed for these estimates.; Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions	Duration of Study (up to 3 years)
Secondary	Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.	The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.; Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.	Duration of study (up to 3 years)