A phase 2 study of Pemetrexed versus Pemetrexed + Erlotinib in second line Treatment for NSCLC

• Conditions: Patients who have histologically or cytologically documented diagnosis of Non Small Cell Lung Cancer (Stage IIIA, IIIB or IV at entry), with progressive disease after treatment with 1 prior chemotherapy regimen, who are considered for second line therapy.; MedDRA version: 8.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOS

• Registration Number: EUCTR2006-005118-11-AT
• Lead Sponsor: Eli lilly and Company Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09-07
• Last Update Posted: 16 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

[1]Histological or cytological diagnosis of NSCLC with locally advanced or metastatic disease (Stage IIIA, IIIB or IV at entry) that is not amenable to curative therapy
[2]Non-smoker and smoker patients
[3]At least one unidimensionally measurable lesion meeting RECIST criteria. Positron emission tomography (PET scans) and ultrasound are not allowed.
[4]Patients must have failed one prior platinum-based chemotherapy regimen and must be considered eligible for further chemotherapy following progression of their disease. Chemotherapy must be completed at least 2 weeks prior to study enrollment and the patient must have recovered from the acute toxic effects of the regimen.
[5]Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis or chest for the treatment of NSCLC is not allowed.
Prior radiotherapy must be completed at least 4 weeks before study enrollment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in this lesion since the end of radiation therapy.
[6]At least 4 weeks since any prior surgery. Patients who, in the opinion of the investigator, have fully recovered from surgery in less than 4 weeks may also be considered for the study.
[7]Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) Scale
[8]Estimated life expectancy of at least 8 weeks.
[9]Patient compliance and geographic proximity that allow adequate follow-up.
[10]Adequate organ function including the following:
•Adequate bone marrow reserve: Absolute neutrophils (segmented and bands) count (ANC) > or =1.5 x 109/L, platelets > or =100 x 109/L, and hemoglobin > or = 9 g/dL
•Hepatic: Bilirubin < or = 1.5 x ULN, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) < or = 3 x ULN (AP, AST and ALT •Renal: Calculated creatinine clearance (CrCl) > or = 45 mL/min based on the standard Cockcroft and Gault formula and serum creatinine <1.5 x ULN
[11]Signed informed consent from patient.
[12]Males or females at least 18 years of age.
[13]For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding.
For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

[14]Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[15]Prior exposure to agents directed at the HER axis (e.g., Gefitinib, Erlotinib, Cetuximab, or Trastuzumab).
[16]Prior exposure to agents directed at Pemetrexed molecular targets (i.e., TS or DHFR inhibitors).
[17]Any known significant ophthalmologic abnormalities of the surface of the eye (The use of contact lenses is not recommended).
[18]Erlotinib and Pemetrexed are contraindicated in patients who have a history of severe hypersensitivity reaction to Erlotinib or Pemetrexed or to any other ingredient used in the formulation.
[19]Recent (within 30 days of enrolment) or concurrent yellow fever vaccination
[20]Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
[21]Patients under therapy with warfarin or coumarin derivatives.
[22]Pregnancy / Breast-feeding.
[23]Have a serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol.
[24]Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
[25]Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin doses < or =1.3 grams per day, for a 5-day period (8-day period for long-acting agents such as piroxicam).
[26]Brain metastasis. Patients who are symptomatic for brain metastasis must have a pretreatment CT or MRI of the brain. A patient with documented brain metastasis at the time of study entry will be excluded from entering in the study. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
[27]Presence of clinically detectable (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
[28]Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease as defined by the New York Heart Association Class III or IV.
[29]Concurrent administration of any other antitumor therapy.
[30]Inability or unwillingness to take folic acid or vitamin B12 supplementation.
[31]Inability to take corticosteroids.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate progression free survival between Pemetrexed 500 mg/m² every 3 weeks + Erlotinib 150 mg daily and Pemetrexed 500 mg/m² every 3 weeks when given as second line therapy for the treatment of locally advanced or metastatic Non Small Cell Lung Cancer ;Secondary Objective: Assess and compare the following variables in both treatment arms:<br>•safety and adverse events profile <br>•response rates <br>•disease control rates (percentage of randomized patients with best response of Stable Disease, Partial Response or Complete Response)<br>•time to treatment failure <br>•overall survival including 1-year survival rates<br>;Primary end point(s): Progression free survival