A Study for Non-Smoker Patients With Nonsquamous Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00550173
• Recruitment Status: Completed
• First Posted: October 29, 2007
• Results First Posted: February 13, 2013
• Last Update Posted: February 13, 2013
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of this study is to compare the combination of erlotinib and pemetrexed versus either pemetrexed alone and erlotinib alone, in terms of progression-free survival (time until the objective worsening of the disease) in patients who have never smoked and have locally advanced or metastatic Nonsquamous Non-Small Cell Lung Cancer who have failed a first-line chemotherapy treatment.

Condition or disease	Intervention/treatment	Phase
Non-Small-Cell Lung Cancer	Drug: pemetrexed; Drug: erlotinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 247 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2 Study Comparing Erlotinib-Pemetrexed, Pemetrexed Alone, and Erlotinib Alone, as Second-Line Treatment for Non-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer
• Study Start Date: November 2007
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: January 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pemetrexed + Erlotinib; Pemetrexed 500 milligrams per meter squared (mg/m^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Drug: pemetrexed; 500 milligrams per meter squared (mg/m^2), intravenous (IV), every (q) 21 days until progression or unacceptable toxicity develops; Other Names: LY231514; Alimta; Drug: erlotinib; 150 mg, orally, once daily until progression or unacceptable toxicity develops
Active Comparator: Erlotinib; Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Drug: erlotinib; 150 mg, orally, once daily until progression or unacceptable toxicity develops
Active Comparator: Pemetrexed; Pemetrexed 500 mg/m^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.	Drug: pemetrexed; 500 milligrams per meter squared (mg/m^2), intravenous (IV), every (q) 21 days until progression or unacceptable toxicity develops; Other Names: LY231514; Alimta

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Randomization to measured PD up to 38 months ]
   PFS is defined as the time from randomization to the first date of progressive disease (PD; either objectively determined or clinical progression) or death from any cause. PD was defined as at least a 20% increase in sum of longest diameter of target lesions as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. Time to disease progression was censored at the date of death.

Secondary Outcome Measures :

1. Percentage of Participants With a Tumor Response of Complete Response (CR) or Partial Response (PR) [Tumor Response Rate (TRR)] [ Time Frame: Randomization to measured disease progression up to 38 months ]
   TRR was defined as the number of responders (complete or partial) divided by the number of participants qualified for tumor response, as assessed using the RECIST version 1.0 guideline, multiplied by 100. RECIST guidelines: CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions.
2. Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause up to 45.5 months ]
   OS is defined as the time from randomization to the date of death from any cause.
3. Number of Participants With Adverse Events [ Time Frame: Randomization up to 39 months ]
   A summary of serious and all other non-serious adverse events (AEs), which include AEs reported for pharmacological toxicity, is located in the Reported Adverse Event module.
4. Percentage of Participants With CR, PR, and Stable Disease (SD) - Disease Control Rate (DCR) [ Time Frame: Randomization to disease progression up to 38 months ]
   DCR was defined as the percentage of participants with CR, PR, or SD divided by the number of randomized and treated participants as assessed using the RECIST criteria. CR was defined as the disappearance of all target lesions; PR was defined as 1) at least a 30% decrease in sum of longest diameter of target lesions or 2) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions; PD was defined as at least a 20% increase in sum of longest diameter of target lesions; SD was defined as small changes that did not meet the above criteria.
5. Time to Worsening of Symptoms (TWS) on Lung Cancer Symptoms Scale (LCSS) [ Time Frame: Randomization to first date of worsening of any of 6 LCSS symptom specific items or up to 12.4 months ]
   TWS assessed using the LCSS a participant rated lung cancer instrument which consisted of 9 disease related symptoms and quality of life (QoL) items, with 6 subscales related to major lung cancer symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 summation items related to QoL (activity status, symptomatic distress, and overall QoL). Each item is marked on a visual analog scale (VAS) 0 (low symptoms/QoL items) to 100 (high symptoms/QoL items). The mean of the 6 subscales is used to calculate the average symptom burden index. TWS was measured from the date of study enrollment to the first date of a worsening in any 1 of the 6 LCSS symptom-specific items (as defined by a VAS 15-mm increase from baseline in the patient-reported score for any of these 6 items).
6. Number of Participants With Mutated or Non-Mutated Epidermal Growth Factor Receptor (EGFR) Genotype Status [ Time Frame: Randomization to date of PD or death up to 38 months ]
   EGFR mutation status was defined as: participants with any mutations detected were categorized as mutated and participants without any mutations detected were categorized as non-mutated.
7. Probability of OS at 12 Months [ Time Frame: Month 12 ]
   OS time is censored at the date of last contact for participants who were still alive or lost to follow-up.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients with locally advanced or metastatic nonsquamous non-small cell lung cancer
• Patients must be non-smokers
• Patients must have at least one measurable lesion
• Performance status of 0 to 2 on the Eastern Cooperative Oncology Group Scale
• Patients must have failed only one prior chemotherapy regimen and must be considered eligible for further chemotherapy following progression of their disease.

Exclusion Criteria:

• Patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication
• Patients who have previously received treatment with drugs against the human epidermal growth factor receptors
• Patients who have previously received treatment with drugs which have similar targets as Pemetrexed
• Patients who have any known significant ophthalmologic abnormalities of the surface of the eye
• Patients who have a history of severe hypersensitivity reaction to erlotinib or pemetrexed

Contacts and Locations

Locations

Brazil

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Barretos, Brazil, 14784700

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Ijui, Brazil, 98700 000

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São Paulo, Brazil, 01277-900

China

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Beijing, China, 100730

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Nanning, China, 530000

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Shanghai, China, 200030

Hong Kong

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Sha Tin, Hong Kong

India

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Ahmedabad, India, 380016

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Bhopal, India, 462001

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Hyderabaad, India, 500082

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Jaipur, India, 302013

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Kochin, India, 682304

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Kolkata, India, 700 026

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Madurai, India, 625020

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Mohali, India, 160062

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Mumbai, India, 400 026

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New Delhi, India, 110017

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Vishakhapatnam, India, 530002

Korea, Republic of

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Jin-Ju-Si, Korea, Republic of, 660-702

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Seoul, Korea, Republic of, 138-736

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Suwon-City, Korea, Republic of, 442-723

Taiwan

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Changhua, Taiwan, 500

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Taichung, Taiwan, 407

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Tao-Yuan, Taiwan, 333

United Kingdom

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Poole, Dorset, United Kingdom, BH15 2JB

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Chelmsford, Essex, United Kingdom, CM1 7ET

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Aberdeen, Scotland, United Kingdom, AB25 2ZN

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Guildford, Surrey, United Kingdom, GU2 7XX

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Manchester, United Kingdom, M20 4BX

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

Additional Information:

Lilly Clinical Trial Registry 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lee DH, Lee JS, Kim SW, Rodrigues-Pereira J, Han B, Song XQ, Wang J, Kim HK, Sahoo TP, Digumarti R, Wang X, Altug S, Orlando M. Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer. Eur J Cancer. 2013 Oct;49(15):3111-21. doi: 10.1016/j.ejca.2013.06.035. Epub 2013 Jul 24.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00550173
• Other Study ID Numbers: 10725; H3E-MC-S103 ( Other Identifier: Eli Lilly and Company )
• First Posted: October 29, 2007
• Results First Posted: February 13, 2013
• Last Update Posted: February 13, 2013
• Last Verified: January 2013

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pemetrexed; Erlotinib Hydrochloride; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors