Pemetrexed or Erlotinib as Second-Line Therapy in Treating Patients With Advanced Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00738881
First received: August 20, 2008
Last updated: January 14, 2013
Last verified: November 2012
  Purpose

This randomized phase III trial is studying pemetrexed to see how well it works compared with erlotinib when given as second-line therapy in treating patients with advanced non-small cell lung cancer. Pemetrexed and erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed is more effective than erlotinib in treating advanced non-small cell lung cancer


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Drug: pemetrexed disodium
Phase 3

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 III Biomarker Validation Study of Second-line Therapy in Patients With Advanced Non- Small Cell Lung Cancer (NSCLC) Randomized to Pemetrexed Versus Erlotinib

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Time from randomization to the first date of documented disease progression or death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier survival curves and a 1-sided stratified log rank test [accounting for all the stratification factors except FISH status and cooperative group] will be used to compare PFS between the erlotinib and pemetrexed arms within the FISH(+) and FISH(-) subgroups. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess whether the distribution of PFS times differ with respect to treatment regimen after having adjusted for the stratification factors as well as other potential prognostic and treatment covariates.


Secondary Outcome Measures:
  • Time to treatment failure [ Time Frame: The time from date of randomization to the date at which the patient is removed from the treatment, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of all time to event data will be estimated using the method of Kaplan-Meier survival curves. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess potential differences in time to event outcomes after adjusting for the stratification factors and other potential prognostic and treatment covariates for these secondary endpoints.

  • Overall survival [ Time Frame: Time from randomization to time of death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test [accounting for all the stratification factors except FISH status and cooperative group] will be used to compare overall survival between the erlotinib and pemetrexed arms within the FISH(+) and FISH(-) subgroups, compare overall and progression free survival between the erlotinib and pemetrexed arms within the subgroups defined on the basis of the EGFR expression by IHC, and EGFR gene mutation status (MUT). Cox proportional hazards model will be used to assess potential differences.

  • Confirmed response rate defined as complete response (CR) or a partial response (PR) per RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. The proportion of patients with confirmed CR and PR will be computed within each treatment arm and exact binomial confidence intervals for the true proportion computed. Chi-square test and Fisher's exact test will be used to compare the response rates between the treatment arms within the subgroups defined by FISH status, IHC, and MUT.

  • Number and severity of adverse events (overall and within each arm) per NCI CTC Version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Will be recorded for each patient and frequency tables will be reviewed to determine the overall patterns. Will be tabulated and summarized within the subgroups defined by FISH status, IHC, and MUT. Grade 3+ adverse events will be similarly described and summarized separately. Overall toxicity incidence will be summarized using frequency distributions, graphical techniques and other descriptive measures. Chi-square test and Fisher's exact test will be used to formally compare the differences in adverse event profiles between the treatment arms within the different subgroups.


Estimated Enrollment: 1196
Study Start Date: October 2008
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral erlotinib hydrochloride 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 pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: pemetrexed disodium
Given IV
Other Names:
  • ALIMTA
  • LY231514
  • MTA

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed non-small cell lung cancer (NSCLC), either oninitial diagnosis or at the time of disease recurrence/progression

    • Mixed histology allowed if all components are consistent with NSCLC
  • Recurrent or progressive disease
  • Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques or as ≥ 1.0 cm by spiral CT scan

    • Measurable disease must be outside of any previously irradiated treatment field(s) unless there is disease progression or recurrence within the irradiated field(s)
    • No nonmeasurable disease only, defined as any of the following:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses not confirmed and followed by imaging techniques
      • Cystic lesions
      • Single disease site in prior radiotherapy field
  • Tumor tissue samples must be available and adequate for epidermal growth factor receptor (EGFR) evaluation by FISH
  • Previously treated with only one cytotoxic chemotherapy regimen for advanced disease

    • Neoadjuvant/adjuvant cytotoxic chemotherapy administered< 12 months (from date chemotherapy was started) prior to study entry will be counted as one prior treatment
    • Neoadjuvant/adjuvant chemotherapy administered ≥ 12 months prior to study entry and use of targeted agents (e.g., monoclonal antibodies) will not be counted as one prior treatment
  • No symptomatic serosal effusion (≥ grade 2 dyspnea as measured by CTCAE v3.0) that is not amenable to drainage
  • No brain metastasis, unless the following criteria are met:

    • Brain metastasis is stable and has been previously treated with either whole-brain radiotherapy or gamma-knife surgery
    • More than 14 days since prior steroid treatment
  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL
  • Total bilirubin normal (ULN) OR direct bilirubinnormal
  • AST and ALT ≤ 2.5 times ULN
  • INR ≤ 1.5
  • Creatinine clearance ≥ 45 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to take folic acid, vitamin B_12 supplementation, and dexamethasone
  • No known HIV positivity
  • No clinically significant infection
  • No impaired gastrointestinal (GI) function, inability to swallow pills in the absence of a feeding tube, or GI disease that may significantly alter absorption of oral medications (e.g., ulcerative disease, uncontrolled nausea and vomiting, malabsorption syndromes, or bowel obstruction)
  • No serious condition that, in the opinion of the investigator, would preclude the patient's ability to complete the study therapy or increase the risk for serious adverse events
  • No other invasive malignant solid tumor or hematologic malignancy, except for any of the following:

    • Prior carcinoma in situ, regardless of organ involvement, or nonmelanoma cutaneous carcinoma that was definitively treated ≥ 3 years ago with no subsequent evidence of recurrence
    • Other prior malignancy diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence

      • Prior breast cancer that was definitively treated > 5 years ago allowed provided patient is not receiving aromatase inhibitors
      • Prio rlow-grade (Gleason score ≤ 6) localized prostate cancer that was diagnosed < 3 years ago allowed

        • Concurrent medications to maintain disease remission allowed
  • No concurrent severe and/or uncontrolled medical condition, including any of the following:

    • Angina pectoris
    • Congestive heart failure within the past 3 months, unless ejection fraction > 40%
    • Myocardial infarction within the past 6 months
    • Cardiac arrhythmia
    • Diabetes mellitus
    • Hypertension
    • Any other severe underlying disease that, in the judgment of the investigator, would preclude study entry
  • No respiratory symptoms > CTCAE grade 1
  • No significant traumatic injury within the past 4 weeks
  • No concurrent prophylactic colony-stimulating factors
  • Recovered from prior radiotherapy, except for alopecia
  • No prior radiotherapy to > 25% of bone marrow
  • No prior EGFR tyrosine kinase inhibitors or pemetrexed disodium
  • More than 3 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
  • More than 2 weeks since prior immunotherapy, gene therapy, or other biologic therapy
  • More than 2 weeks since prior limited-field radiotherapy (4 weeks for full-field radiotherapy)
  • More than 2 weeks since prior minor surgery*
  • More than 4 weeks since prior major surgery (i.e., laparotomy)* or open biopsy
  • More than 4 weeks since prior hormonal therapy
  • More than 4 weeks since prior and no other concurrent ancillary therapy considered investigational (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation)
  • No aspirin dose ≥ 1.3 g/day for ≥ 10days before, during, and for ≥ 10 days after treatment with pemetrexed disodium
  • No other concurrent chemotherapy, immunotherapy, hormonal therapy, or radiotherapy

    • Radiotherapy for symptom palliation (e.g., painful pre-existing bony metastasis) allowed
  • No other concurrent anticancer therapy
  • No concurrent major surgery
  • No concurrent antiretroviral therapy
  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: NCT00738881

  Show 268 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Investigators
Principal Investigator: Alex Adjei North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00738881     History of Changes
Other Study ID Numbers: NCI-2009-00663, N0723, U10CA025224, CDR0000612010
Study First Received: August 20, 2008
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Folic Acid Antagonists
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014