A Study of Pemetrexed and Gefitinib Versus Gefitinib in Non-Small Cell Lung Cancer (NSCLC)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01469000
First received: November 8, 2011
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to compare the combination of pemetrexed and gefitinib versus gefitinib alone, in terms of progression-free survival. This study is in participants who have stage IV non squamous NSCLC with activating epidermal growth factor mutations and who have not had any previous chemotherapy for stage IV disease.


Condition Intervention Phase
Carcinoma, Non Small Cell Lung
Drug: Pemetrexed
Drug: Gefitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Phase 2 Trial of Pemetrexed and Gefitinib Versus Gefitinib as First Line Treatment for Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Randomization to first date of objective disease progression or death from any cause (follow up assessments until death or until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progressive disease [ Time Frame: Randomization to first date of objective disease progression from any cause (follow up assessments until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Randomization to date of death from any cause (follow up assessments until death or until end of study, estimated up to 30 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]
  • Overall response rate [ Time Frame: Randomization to date of objective disease progression (follow up assessments until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]
  • Disease control rate [ Time Frame: Baseline to objective disease progression (follow up assessments until death or until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Baseline to objective disease progression or death (follow up assessments until death or until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]
  • Symptom control [ Time Frame: Baseline to objective disease progression (follow up assessments until death or until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]
  • Time to worsening of symptoms using the Lung Cancer Symptom Scales (LCSS) [ Time Frame: Baseline to objective disease progression (follow up assessments until death or until end of study, estimated up to 18 months from Last Participant Entered Treatment) ] [ Designated as safety issue: No ]

Estimated Enrollment: 188
Study Start Date: February 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gefitinib
Single agent gefitinib (250 mg/day)
Drug: Gefitinib
250 mg, orally once per day. Number of cycles until disease progression or unacceptable toxicity develops.
Other Name: Iressa
Active Comparator: Gefitinib-pemetrexed combination
Concurrent treatment with gefitinib (250 mg/day) and pemetrexed (500 mg/m^2 on Day 1 of every 21 day cycle)
Drug: Pemetrexed
500 mg/m^2, intravenous (in the vein) on day 1 of each 21 day cycle. Number of cycles until disease progression or unacceptable toxicity develops.
Other Name: Alimta
Drug: Gefitinib
250 mg, orally once per day. Number of cycles until disease progression or unacceptable toxicity develops.
Other Name: Iressa

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced (Stage IV) or recurrent non-squamous NSCLC
  • Eligible participants of reproductive potential must agree to use adequate contraceptive methods during the study period and for at least 6 months after the last dose of study therapy
  • Negative pregnancy test for women of childbearing potential
  • Males or females, aged 18 years or above
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • The participant's primary NSCLC tumor has an activating Epidermal Growth Factor Receptor (EGFR) mutation, as determined by any validated method
  • The participant consents to provide a tissue sample for prestudy EGFR mutation testing and the tumor tissue sample is available for detection of EGFR expression and other markers for centralized testing by Lilly
  • The participant has measurable disease at the time of study entry, documented by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • The participant has not had any prior systemic chemotherapy, immunotherapy, or biological therapy (for example, targeted therapy, such as erlotinib or gefitinib) for Stage IV or recurrent non-squamous NSCLC
  • The participant has adequate organ function, defined as:

    • White blood cell count ≥3 x 10^9/L; absolute neutrophil count (segmented and bands) ≥1.5 x 10^9/L; platelet count ≥100 x 10^9/L; hemoglobin ≥9.0 g/dL
    • Total bilirubin ≤1.5 times the upper limit of the normal (ULN) range; and alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times ULN (or ≤5 times ULN if the liver has tumor involvement)
    • Calculated creatinine clearance ≥45 mL/min
  • The participant is able to take folic acid, vitamin B12, and dexamethasone, according to the protocol's requirements
  • Life expectancy of at least 3 months
  • Provision of informed consent
  • Prior radiation therapy is allowed to <25% of the bone marrow; however, prior radiation to the whole pelvis not allowed. Prior radiation therapy must be completed at least 2 weeks prior to first study-drug administration. Participants must have recovered from the acute toxic effects prior to first study-drug administration.

Exclusion Criteria:

  • The participant has received prior chemotherapy for advanced and/or metastatic disease, or adjuvant/neoadjuvant treatment with pemetrexed or an EGFR-tyrosine Kinase inhibitor (TKI)
  • The participant`s tumor contains predominantly small cell lung cancer or squamous NSCLC
  • The participant is receiving concurrent treatment with any other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, chemoembolization, biological or targeted therapy, or radiotherapy (palliative irradiation of bone lesions is allowed)
  • The participant has untreated central nervous system (CNS) metastases Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radiosurgery) ending at least 2 weeks before enrollment, or after surgical resection performed at least 28 days before enrollment. No evidence of Grade ≥1 CNS hemorrhage based on pretreatment MRI or Intravenous (IV) contrast CT scan (performed within 21 days before randomization).
  • The participant has undergone radiotherapy within 28 days before enrollment (localized radiotherapy for pain relief allowed, provided 25% or less of their total bone marrow had been irradiated)
  • The participant has clinically relevant congestive heart failure (New York Heart Association [NYHA] II-IV) or symptomatic or poorly controlled cardiac arrhythmia
  • The participant has a serious illness or medical condition that would compromise their safety or impair their ability to comply with the protocol's requirements, including, but not limited to, the following:

    • Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
    • Active or uncontrolled clinically serious infection
    • Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study
    • Uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain
    • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the participant ineligible for entry into this study
    • The participant has significant third space fluid retention, and is not amenable for required repeated drainage
    • Known allergy or hypersensitivity reaction to any of the treatment components
  • Are unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed
  • Concomitant use of cytochrome P450 (CYP)3A4 inducers or CYP3A4 inhibitors
  • Participants under therapy with warfarin or coumarin derivatives who are unable to switch to low molecular weight heparin, unless regular monitoring of changes in prothrombin time (PT) (PT/international normalized ratio [INR]) will be applicable
  • Any known significant ophthalmologic abnormalities of the surface of the eye. The use of contact lenses is not recommended during the study
  • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Participants participating in surveys or observational studies are eligible to participate in this study
  • The participant has previously received treatment with gefitinib, erlotinib or pemetrexed
  • Any evidence of clinically active interstitial lung disease. Asymptomatic participants with chronic, stable, radiographic changes are eligible.
  • Have preexisting idiopathic pulmonary fibrosis as evidenced by computed tomography (CT) scan/x-ray at baseline; have or had any disease of acute lung injury, idiopathic pulmonary fibrosis, pulmonary pneumonia, or pneumoconiosis evident on an x-ray; have or had any disease of radiation pneumonia or drug-induced pneumonia, which requires treatment with corticosteroids.
  • The participant is pregnant or breastfeeding
  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: NCT01469000

Locations
China
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Beijing, China, 100036
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Changchun, China, 130012
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Changsha, China, 410013
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Guang Zhou, China, 510120
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Sichuan, China, 610041
Japan
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Aichi, Japan, 464-8681
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Chiba, Japan, 277 8577
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Hyogo, Japan, 650-0046
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Kanagawa, Japan, 228-0329
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Okayama, Japan, 710-8602
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Osaka, Japan, 589-8511
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Shizuoka, Japan, 411-8777
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Tokyo, Japan, 104-0045
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Yamaguchi, Japan, 755-0241
Korea, Republic of
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Cheong Ju-City, Korea, Republic of, 361-711
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Incheon, Korea, Republic of, 405-760
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Seoul, Korea, Republic of, 135 720
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Suwon-City, Korea, Republic of, 442-723
Taiwan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Jhonghe City, Taiwan, 235
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Kaohsiung, Taiwan, 824
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Keelung, Taiwan, 204
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Kuei Shan Hsiang, Taiwan, 33305
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Niao Sung Hsiang, Taiwan, 833
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Taichung, Taiwan, 40705
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Taipei, Taiwan, 100
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01469000     History of Changes
Other Study ID Numbers: 14034, H3E-CR-JMIT(a)
Study First Received: November 8, 2011
Last Updated: July 11, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Department of Health
China: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
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
Pemetrexed
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014