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Trial record 1 of 1 for:    N0723
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Pemetrexed Disodium or Erlotinib Hydrochloride as Second-Line Therapy in Treating Patients With Advanced Non-small Cell Lung Cancer (MARVEL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00738881
Recruitment Status : Terminated (Slow accrual)
First Posted : August 21, 2008
Results First Posted : October 2, 2014
Last Update Posted : October 29, 2015
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Southwest Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase III trial studies pemetrexed disodium to see how well it works compared with erlotinib hydrochloride as second-line therapy in treating patients with non-small cell lung cancer that has spread to other places in the body. Pemetrexed disodium and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pemetrexed disodium is more effective than erlotinib hydrochloride in treating advanced non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Recurrent Non-Small Cell Lung Carcinoma 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MARVEL: Marker Validation of Erlotinib in Lung Cancer- 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
Study Start Date : October 2008
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm I (erlotinib hydrochloride)
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
  • OSI-774
  • Tarceva

Experimental: Arm II (pemetrexed disodium)
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
  • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Time from randomization to the first date of documented disease progression or death, assessed up to 5 years ]
    Estimated using the method of Kaplan-Meier survival curves to compare PFS between the erlotinib and pemetrexed arms using an intent-to-treat (ITT) analysis. Due to the small sample size (21 of the required 954 patients ~2%), analyses within the FISH(+) and FISH(-) groups were not performed, and no formal analyses for the primary or the secondary efficacy outcomes were performed.

Secondary Outcome Measures :
  1. 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 ]
    The distribution of all time to event data will be estimated using the method of Kaplan-Meier survival curves.

  2. Overall Survival [ Time Frame: Time from randomization to time of death from any cause, assessed up to 5 years ]
    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 epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC), and EGFR gene mutation status (MUT). Cox proportional hazards model will be used to assess potential differences.

  3. Confirmed Response Rate Defined as Complete Response (CR) or a Partial Response (PR) Per Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Up to 5 years ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Documented recurrence or disease progression of NSCLC

    • NSCLC must be confirmed by pathologic examination, either on initial diagnosis or disease recurrence/progression; mixed histology allowed if all components consistent with NSCLC
  • 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 computed tomography (CT); if spiral CT is used, it must be used for both pre- and post- treatment tumor assessments
  • Prior radiation therapy is permitted as long as:

    • Recovered from the toxic effects of radiation treatment before study entry, except for alopecia
    • =< 25% of bone marrow radiated
    • Presence of measurable disease whether in-field disease progression/recurrence or disease outside the treatment fields of radiation port
  • Absolute neutrophil count (ANC) >= 1,500 uL
  • Platelet (PLT) >= 100,000 uL
  • Hemoglobin (Hgb) >= 10 g/dL
  • Total bilirubin: within normal institutional limits (WNL) OR direct bilirubin =< upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • International normalized ratio (INR) =< 1.5
  • Calculated creatinine clearance >= 45 mL/min using the Cockcroft-Gault formula
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Negative pregnancy test done =< 7 days prior to pre-registration, for women of childbearing potential only
  • Ability to provide informed consent
  • Life expectancy >= 12 weeks
  • Tissue available and willing to submit tissue for central pathology review and EGFR evaluation; performed on original diagnostic/recurrent tissue (preferably paraffin-embedded tissue blocks); if institution unable to release tissue blocks, willing to submit 25 unstained slides (15 sections cut at 5 microns mounted on charged slides and 10 sections cut at 10 microns mounted on uncharged slides)
  • Must be previously treated for advanced disease with only 1 chemotherapy regimen which must contain cytotoxic agent(s); adjuvant/neoadjuvant treatment with cytotoxic agent(s) administered < 12 months (from date chemotherapy was started) prior to pre-registration will be considered as one prior treatment; NOTE: adjuvant/neoadjuvant treatment administered >= 12 months, use of targeted agents such as monoclonal antibodies prior to pre-registration will NOT be counted as one prior treatment; patient could have had adjuvant/neoadjuvant chemotherapy >= 12 months and 1 systemic chemotherapy regimen for metastatic or recurrent disease
  • Able to take folic acid, vitamin B12 supplementation, and dexamethasone
  • Able to permanently discontinue aspirin dose of >= 1.3 grams/day >= 10 days before and after pemetrexed treatment
  • Fertile patients must use effective contraception
  • Able to take folic acid, vitamin B_12 supplementation, and dexamethasone
  • Stable brain metastasis that have been treated with either whole brain radiation therapy or gamma knife surgery and are off steroid treatment for > 14 days prior to pre-registration, if applicable
  • Willingness to return to enrolling institution for treatment and follow-up

Exclusion Criteria:

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Any clinically significant infection, at the treating physician's discretion
  • Known human immunodeficiency virus (HIV) positive patients
  • Impairment of 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, bowel obstruction, etc)
  • Serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study or increase the risk for serious adverse events
  • Any of the following prior therapies:

    • Prior radiation to > 25% of bone marrow
    • EGFR tyrosine kinase inhibitors
    • Pemetrexed
    • Chemotherapy =< 3 weeks prior to pre-registration
    • Mitomycin C/nitrosoureas =< 6 weeks prior to pre-registration
    • Immunotherapy =< 2 weeks prior to pre-registration
    • Biologic therapy =< 2 weeks prior to pre-registration
    • Gene therapy =< 2 weeks prior to pre-registration
    • Full field radiation therapy =< 4 weeks prior to pre-registration
    • Limited field radiation therapy =< 2 weeks prior to pre-registration
    • Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to pre-registration or anticipation of need for major surgical procedure during the course of the study; minor surgery =< 2 weeks prior to pre-registration; insertion of a vascular access device is not considered major or minor surgery in this regard
  • Other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) =< 4 weeks prior to pre-registration
  • Steroid therapy for brain metastasis =< 14 days prior to pre-registration
  • Symptomatic serosal effusion (>= Common Terminology Criteria for Adverse Events [CTCAE] v3.0 grade 2 dyspnea) that is not amenable to drainage prior to pre-registration
  • Other invasive solid or hematologic malignancy; exceptions: prior malignancy was diagnosed and definitively treated >= 5 years previously with no subsequent evidence of recurrence; patients with a history of low-grade (Gleason score =< 6) localized prostate cancer will be eligible even if diagnosed < 3 years prior to pre-registration; these patients may continue on medications concomitantly to maintain their disease remission as necessary; patients with carcinoma in situ, regardless of organ involvement, or non-melanoma cutaneous carcinomas are eligible if these were definitively treated >= 3 years previously with no subsequent evidence of recurrence; Note: patients with breast cancer that was definitively treated > 5 years earlier but continue to receive aromatase inhibitors are NOT eligible
  • Only non-measurable disease, defined as all other lesions, including small lesions whose longest diameter measures < 2 cm with conventional techniques or < 1.0 cm with spiral CT, and truly non-measurable lesions, which include the following as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria dated June 1999:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Single disease site in prior radiation field
  • Any of the following concurrent severe and/or uncontrolled medical conditions:

    • Angina pectoris
    • History of congestive heart failure =< 3 months prior to pre-registration, unless ejection fraction > 40%
    • Myocardial infarction =< 6 months prior to pre-registration
    • Cardiac arrhythmia
    • Diabetes mellitus
    • Hypertension
    • Any other severe underlying diseases which are, in the judgment of the investigator, inappropriate for entry into this study
  • Respiratory symptoms > CTCAE grade 1

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00738881

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Sponsors and Collaborators
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Southwest Oncology Group
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Principal Investigator: Alex Adjei Alliance for Clinical Trials in Oncology
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00738881    
Other Study ID Numbers: NCI-2009-00663
NCI-2009-00663 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N0723 ( Other Identifier: Alliance for Clinical Trials in Oncology )
N0723 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA025224 ( U.S. NIH Grant/Contract )
First Posted: August 21, 2008    Key Record Dates
Results First Posted: October 2, 2014
Last Update Posted: October 29, 2015
Last Verified: December 2014
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors