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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Adenocarcinoma; Minimally Invasive Lung Adenocarcinoma; Malignant Pleural Effusion; Stage IIIB Lung Non-Small Cell Cancer AJCC v7; Stage IV Lung Non-Small Cell Cancer AJCC v7; Malignant Pericardial Effusion; Lung Adenosquamous Carcinoma
• Intervention / Treatment: Drug: Erlotinib Hydrochloride; Drug: Carboplatin; Drug: Paclitaxel; Drug: Erlotinib

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.

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Castro Valley, California, United States, 94546
      • East Bay Radiation Oncology Center
    • Castro Valley, California, United States, 94546
      • Valley Medical Oncology Consultants-Castro Valley
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Fremont, California, United States, 94538
      • Valley Medical Oncology Consultants-Fremont
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Hematology and Oncology Associates-Oakland
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • Tom K Lee Inc
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Pleasanton, California, United States, 94588
      • Valley Care Health System - Pleasanton
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Diego, California, United States, 92161
      • Veterans Administration-San Diego Medical Center
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Pablo, California, United States, 94806
      • Doctors Medical Center- JC Robinson Regional Cancer Center
  • Connecticut
    • Middletown, Connecticut, United States, 06457
      • Middlesex Hospital
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • La Grange, Illinois, United States, 60525
      • AMITA Health Adventist Medical Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Danvers, Massachusetts, United States, 01923
      • Mass General/North Shore Cancer Center
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
    • South Weymouth, Massachusetts, United States, 02190
      • South Shore Hospital
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Columbia, Missouri, United States, 65201
      • Veterans Administration
    • Jefferson City, Missouri, United States, 65101
      • Capital Region Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health Callahan Cancer Center
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Hampshire
    • Nashua, New Hampshire, United States, 03060
      • Saint Joseph Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Lake Success, New York, United States, 11042
      • Northwell Health NCORP
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10035
      • Ralph Lauren Center for Cancer Care and Prevention
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • Syracuse, New York, United States, 13203
      • Saint Joseph's Hospital Health Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Wilson, North Carolina, United States, 27893
      • Wilson Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Cancer Care Associates
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Kilmarnock, Virginia, United States, 22482
      • Rappahannock General Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (erlotinib hydrochloride); Patients receive erlotinib hydrochloride PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Erlotinib Hydrochloride; Given PO; Other Names: Cp-358,774; Tarceva; OSI-774; Drug: Erlotinib; Given PO
Experimental: Arm II (erlotinib hydrochloride, paclitaxel, carboplatin); Patients receive erlotinib hydrochloride as in arm I. Patients also receive paclitaxel 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.	Drug: Erlotinib Hydrochloride; Given PO; Other Names: Cp-358,774; Tarceva; OSI-774; Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Erlotinib; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Pasi A Janne, Alliance for Clinical Trials in Oncology

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2005
• Primary Completion (Actual): June 30, 2010
• Study Completion (Actual): November 28, 2017

Study Registration Dates

• First Submitted: August 2, 2005
• First Submitted That Met QC Criteria: August 2, 2005
• First Posted (Estimate): August 4, 2005

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: July 24, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: A Phase II Randomized Study of OSI-774
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Neoplasms, Complex and Mixed; Pleural Neoplasms; Adenocarcinoma; Carcinoma, Adenosquamous; Adenocarcinoma of Lung; Pleural Effusion, Malignant; Pleural Effusion; Adenocarcinoma, Bronchiolo-Alveolar; Pericardial Effusion; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Erlotinib Hydrochloride; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NCI-2009-00464 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000437097; CALGB-30406 (Other Identifier: CTEP)