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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00126581
First received: August 2, 2005
Last updated: September 15, 2014
Last verified: June 2014
  Purpose

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 or by stopping them from dividing. Giving erlotinib hydrochloride together with carboplatin and paclitaxel may kill more tumor cells.


Condition Intervention Phase
Adenocarcinoma of the Lung
Adenosquamous Cell Lung Cancer
Bronchoalveolar Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Drug: paclitaxel
Drug: carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 18 Weeks Progression Free Survival (PFS) Rate [ Time Frame: At 18 weeks ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: Duration of Study (up to 3 years) ] [ Designated as safety issue: No ]

    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


  • Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment. [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: Yes ]

    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.



Other Outcome Measures:
  • Overall Survival [ Time Frame: Time from randomization to death (up to 3 years) ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival (PFS) by Epidermal Growth Factor Receptor (EGFR) Mutation Status [ Time Frame: Duration of treatment (up to 3 years) ] [ Designated as safety issue: No ]

    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.


  • Overall Response Rate by EGFR Mutation Status [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]
    Response and EGFR mutation status are defined in previous outcome measures.

  • Progression Free Survival With KRAS Mutation Status [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]
    Progression free survival is defined in previous outcome measures. GIven the small number of KRAS mutant participants, the analysis combines data from both arms.

  • Overall Response Rate With KRAS Mutational Status [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]
    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.


Enrollment: 188
Study Start Date: August 2005
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Experimental: Arm II
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 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses of treatment, patients may continue to receive erlotinib hydrochloride alone as above.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin

Detailed Description:

PRIMARY OBJECTIVES:

I. 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: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses 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 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00126581

  Show 78 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Pasi Janne Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00126581     History of Changes
Other Study ID Numbers: NCI-2009-00464, NCI-2009-00464, CDR0000437097, CALGB 30406, CALGB-30406, U10CA031946, P30CA014236
Study First Received: August 2, 2005
Results First Received: October 7, 2013
Last Updated: September 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
A Phase II Randomized Study of OSI-774

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Erlotinib
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014