Erlotinib With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III or Stage 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: January 8, 2013
Last verified: January 2013
  Purpose

This randomized phase II trial is studying how well giving erlotinib alone or together with carboplatin and paclitaxel works in treating patients with stage III or stage IV non-small cell lung cancer. Erlotinib 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 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
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; IND# 63,383) 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:
  • Progression-free survival (PFS) rate [ Time Frame: At 18 weeks ] [ Designated as safety issue: No ]
    The product limit estimator developed by Kaplan and Meier will be used to graphically describe progression free survival for patients randomized to each study arm.


Secondary Outcome Measures:
  • Response rate [ Time Frame: 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.

  • Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    The toxicity associated with each treatment regimen will be summarized. For each type of toxicity, a patient's worst treatment-related toxic episode will be used to summarize distribution of toxicity grade experienced.

  • Mutations in EGFR and K-ras [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Univariate analysis will be performed using a log rank test to correlate mutations (EGFR and K-ras) with the PFS. A Cox proportional hazard regression in a multivariable fashion will be used to correlate mutations with survival while adjusting for other prognostic factors. The frequency of tumor response by mutations will be tabulated and their association will be tested by Fisher's exact method. Logistic regression will be used to explore the joint effects of mutations as well as other prognostic factors on tumor response.

  • Mutations in ErbB-2 and B-raf [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The association of ErbB-2 and B-raf mutations with response to OSI-774 (erlotinib) or OSI-774 (erlotinib)/chemotherapy will be tested by Fisher's exact test.


Estimated Enrollment: 180
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 oral erlotinib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Experimental: Arm II
Patients receive erlotinib 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 alone as above
Drug: erlotinib hydrochloride
Given orally
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 progression-free survival of patients with chemotherapy-naïve select stage IIIB or stage IV non-small cell lung cancer treated with erlotinib with or without carboplatin and paclitaxel.

SECONDARY OBJECTIVES:

I. Determine the radiographic response rate in patients treated with these regimens.

II. Correlate the frequency of epidermal growth factor receptor (EGFR) mutations and K-ras mutations with the response rate and time to progression in patients treated with these regimens.

III. Determine the median and overall survival of patients treated with these regimens.

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

ARM I: Patients receive oral erlotinib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive erlotinib 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 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:

  • Renal: Creatinine =< 1.5 mg/dL
  • Histologically confirmed primary non-small cell lung cancer (NSCLC)
  • Adenocarcinoma histology, including any of the following histologic variants: pure or mixed bronchoalveolar cell carcinoma, adenosquamous cell carcinoma
  • No NSCLC not otherwise specified
  • Pathology block or unstained slides from initial or subsequent diagnosis available
  • At least a core biopsy required
  • Fine needle aspirate alone is not sufficient
  • Meets 1 of the following stage criteria: s

    • elect stage IIIB disease with cytologically documented malignant pleural or
    • pericardial effusion or stage IV disease
  • Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
  • The following are considered non-measurable disease:

    • bone lesions,
    • leptomeningeal disease;
    • ascites;
    • pleural or pericardial effusion;
    • lymphangitis cutis/pulmonis;
    • abdominal masses not confirmed and followed by imaging techniques;
    • cystic lesions
  • Meets 1 of the following criteria for smoking history:

    • non-smoker,
    • defined as a person who smoked =< 100 cigarettes in their lifetime;
    • former light smoker,
    • defined as a person who smoked =< 10 pack years AND
    • quit smoking >= 1 year ago
  • No uncontrolled CNS metastases (i.e., any known CNS lesion that is radiographically unstable, symptomatic, and/or requires corticosteroids)
  • ECOG 0-1
  • Hematopoietic:

    • Granulocyte count >= 1,500/mm^3;
    • Platelet count >= 100,000/mm^3;
    • Hemoglobin >= 9.0 g/dL
  • Hepatic:

    • AST =< 2.5 times upper limit of normal (ULN);
    • Total bilirubin =< ULN
  • Gastrointestinal:

    • Able to swallow tablets intact or dissolved in water;
    • no dysphagia;
    • no active gastrointestinal disease or disorder that would alter gastrointestinal motility or absorption;
    • no lack of integrity of the gastrointestinal tract
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior trastuzumab (Herceptin) or cetuximab
  • No prior chemotherapy, including neoadjuvant or adjuvant chemotherapy
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy except for the following:

    • hormones for non-disease-related conditions (e.g., insulin for diabetes);
    • steroids for adrenal failure;
    • intermittent use of dexamethasone as an antiemetic or to prevent paclitaxel hypersensitivity reactions
  • At least 3 weeks since prior radiotherapy, including cranial irradiation
  • No concurrent radiotherapy, including palliative radiotherapy
  • At least 3 weeks since prior major surgery
  • No prior significant surgical resection of the stomach or small bowel
  • No prior erlotinib, gefitinib, or lapatinib
  • No other prior treatment targeting the HER family axis
  • More than 4 weeks since prior and no other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00126581

  Show 79 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, CALGB-30406, U10CA031946, CDR0000437097
Study First Received: August 2, 2005
Last Updated: January 8, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 17, 2014