Pemetrexed Plus Cetuximab in Patients With Recurrent Non Small Cell Lung Cancer

Study Overview
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Brief Summary
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Both pemetrexed and cetuximab have single agent activity in NSCLC and non-overlapping toxicity profiles. While 2-drug combination therapy has proven superior to single agent therapy in the first-line setting of NSCLC, no such phase III trials have been reported in the second-line setting. Therefore, the purpose of this study is to determine the feasibility of combining these drugs, assessing the toxicity profile, determining the MTD and evaluating the activity of the combination in an expanded phase II setting. If the combination appears to have promising activity, further evaluation of this regimen may be warranted comparing it to single agent pemetrexed or cetuximab alone.

Detailed Description
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OUTLINE: This is a multi-center study. Week 1 (day 1): Cetuximab 400mg/m2 Week 2 (Cycle 1, Day 1): Cetuximab 250mg/m2 plus premetrexed at the assigned dose level. Patients will be treated with cetuximab on day 1, 8, 15 of each 21 day cycle. Patients will be treated with pemetrexed on day 1 of each 21 day cycle for a maximum of 6 cycles. Acceptable toxicity and SD, PR or CR: treat up to 6 cycles then continue cetuximab weekly until PD or excess toxicity Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: ANC > 1,500/mm3 Platelets > 100,000/mm3 Hepatic: Bilirubin less than or equal to the upper limit of normal (ULN) Aspartate aminotransferase (AST) < 1.5 X ULN. AST may be < 5 X ULN for patients with liver metastases Alkaline phosphatase < 5 X ULN Renal: Calculated creatinine clearance > 45 mL/min (by Cockcroft-Gault) Cardiovascular: No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, and congestive heart failure) Pulmonary: Not specified

Official Title
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A Phase I-IIa Dose-Ranging Study of Pemetrexed (Alimta) Plus Cetuximab (Erbitux) in Patients With Recurrent Non-Small Cell Lung Cancer (NSCLC): Hoosier Oncology Group LUN04-79

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of NSCLC Recurrent or metastatic disease that is not amenable to curative therapyMeasurable disease according to RECIST At least one prior platinum containing regimen for either locally advanced or metastatic disease Prior chemotherapy must be completed at least 21 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxicity effects of the regimen Ability and willingness to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period Prior radiation therapy allowed to < 25% of the bone marrow Negative pregnancy test Exclusion Criteria: No active infection that in the opinion of the investigator would compromise the subject's ability to tolerate therapy. No serious concomitant systemic disorders that would compromise the safety of the subject or compromise the subject's ability to complete the study, at the discretion of the investigator. No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for at least 2 years. No major thoracic or abdominal surgery within 30 days prior to being registered for protocol therapy. No current breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Treatment<br>Pemetrexed + cetuximab for patients with recurrent non-small cell lung cancer. | Drug: Pemetrexed<br>* Pemetrexed at the assigned dose, day 1 of each 21 day cycle for a maximum of 6 cycles<br>Drug: Cetuximab<br>* Cetuximab 400 mg/m2, week 1, day 1 Cetuximab 250 mg/m2, day 1, 8, 15 of each 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cetuximab | The primary objective of the phase I portion of this study is to define the maximum tolerated dose (MTD) of the combination of pemetrexed and cetuximab | 12 months | 
| Time To Progression (TTP) | The primary objective of the phase II portion is to estimate the time to progression of this combination, evaluated per RECIST criteria where PD= at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Survival Time |  | 24 Months | 
| Toxicity and Safety Profile |  | 12 months | 
| Clinical Benefit Rate | Clinical Benefit Rate (CR + PR + SD lasting more than 90 days) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer