Conditions

Carcinoma, Non Small Cell Lung

Outcome Measures

Primary Outcomes (1)

Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first date of objectively determined progressive disease or death from any cause,whichever is earlier.The censoring is taken in the following order: If a participant didn't have a complete baseline disease assessment,then the PFS time was censored at the enrollment date, regardless of whether or not objectively determined disease progression or death has been observed for the participant;otherwise,if a participant is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis,the PFS time will be censored at the last complete objective progression-free disease assessment date.Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study. Also,the sum must also demonstrate an absolute increase of at least 5 millimeter (mm).The appearance of one or more new lesions is also considered progression.
Randomization to Progressive Disease or Death Due to Any Cause (Up to 58.78 Months)

Secondary Outcomes (6)

Time To Progressive Disease (TTPD)
Randomization to Progressive Disease (Up To 58.78 Months)
Overall Survival (OS)
Randomization to Date of Death Due to Any Cause (Up To 67.12 Months)
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
Randomization to Progressive Disease (Up to 57.36 Months)
Percentage of Participants With CR, PR, and Stable Disease (SD) (Disease Control Rate [DCR])
Randomization to Progressive Disease (Up To 57.36 Months)
Duration of Response (DoR)
First Observation of CR or PR to Progressive Disease or Death Due to Any Cause (Up To 57.36 Months)
+1 more secondary outcomes

Study Arms (2)

250 mg Gefitinib/500 mg Pemetrexed

EXPERIMENTAL

250 milligrams (mg) Gefitinib taken orally once daily (QD) and 500 milligrams per square meter (mg/m²) Pemetrexed taken intravenously (IV) once every 3 weeks concurrently with Gefitinib taken orally QD.

Drug: GefitinibDrug: Pemetrexed

250 mg Gefitinib

ACTIVE COMPARATOR

250 milligrams (mg) Gefitinib taken orally QD

Drug: Gefitinib

Interventions

GefitinibDRUG

250 mg orally once per day. Number of cycles until disease progression or unacceptable toxicity develops.

Also known as: Iressa

250 mg Gefitinib250 mg Gefitinib/500 mg Pemetrexed

PemetrexedDRUG

500 mg/m² IV on day 1 of each 21 day cycle. Number of cycles until disease progression or unacceptable toxicity develops.

Also known as: Alimta

250 mg Gefitinib/500 mg Pemetrexed

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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/liter (L); absolute neutrophil count (segmented and bands) ≥1.5 x 10\^9/L; platelet count ≥100 x 10\^9/L; hemoglobin ≥9.0 gram per deciliter (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 milliliter per minute (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
+2 more criteria

You may not qualify if:

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
+8 more criteria

Contact the study team to confirm eligibility.