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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

Phase 2
18 Years
Open (Enrolling)
Carcinoma, Non Small Cell Lung

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Trial Information

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

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival

Outcome 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)

Safety Issue:


Principal Investigator

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)

Investigator Role:

Study Director

Investigator Affiliation:

Eli Lilly and Company


Japan: Pharmaceuticals and Medical Devices Agency

Study ID:




Start Date:

February 2012

Completion Date:

January 2016

Related Keywords:

  • Carcinoma, Non Small Cell Lung
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms