Dosage Schedule Study of Pemetrexed Monochemotherapy for Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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Patients affected by non-small cell lung cancer (NSCLC) will be treated in pemetrexed monochemotherapy regimen for a maximum of 8 cycles. Pemetrexed is an enhancer of some biomolecules involved in the gemcitabine mechanism of action. Purpose of the trial is to monitor the blood values of these biomolecules at different time intervals, to optimize the synergism between pemetrexed and gemcitabine.

Official Title
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Pemetrexed Monochemotherapy in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer. A Pilot Study to Define the Best Dosing Schedule for a Planned Phase II Randomized Trial

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed - Before Protocol Amendment
* Drug: Pemetrexed - After Protocol Amendment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically or cytologically proven IIIB and IV NSCLC. No symptomatic uncontrolled brain metastasis Not suitable for platinum containing regimens if chemo-naive Performance status less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) Scale. Creatinine Clearance (CrCl) greater than or equal to 45 milliliters per min (mL/min) Exclusion Criteria Prior radiation to greater than 25% of bone marrow Inability to interrupt Aspirin at doses of greater than 1.3 grams/day or non-steroidal anti-inflammatory agents for a 5-day period. Presence of clinically relevant third-space fluid collections not controllable. Significant cardiac disease

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed - Before Protocol Amendment<br> | Drug: Pemetrexed - Before Protocol Amendment<br>* 500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles or disease progression, unacceptable toxicity or patient decision to discontinue<br>* Other names: Alimta;|
| Experimental: Pemetrexed - After Protocol Amendment<br> | Drug: Pemetrexed - After Protocol Amendment<br>* 500 milligrams per square meter (mg/m2), intravenous (IV), every 21 days x 6 cycles or disease progression, unacceptable toxicity or patient decision to discontinue.<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Deoxycytidine Kinase (dCK) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3 | dCK and hENT expression (see Outcome #2) on normal lymphocytes were measured after Pemetrexed administration to evaluate if there was reproducible timing of maximum dCK expression, and to assess proper time interval between pemetrexed and gemcitabine for treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC). Values are calculated as ratio between thereshold cycles (number of polymerase chain reaction [PCR] cycles) with respect to a reference gene; in this case glyceraldehyde 3-phosphate dehydrogenase (GAPDH). | pre-dose, 1, 2, 4, 6, 24, and 48 hours post-dose (3 cycles) | 
| Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3 | dCK (see Outcome #1)and hENT expression (see Outcome #2) on normal lymphocytes were measured after Pemetrexed administration to evaluate if there was reproducible timing of maximum dCK expression, and to assess proper time interval between pemetrexed and gemcitabine for treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC). Values are calculated as ratio between thereshold cycles (number of polymerase chain reaction [PCR] cycles) with respect to a reference gene; in this case glyceraldehyde 3-phosphate dehydrogenase (GAPDH). | pre-dose, 1, 2, 4, 6, 24, and 48 hours post-dose (3 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Objective Tumor Response | Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. | baseline to measured response (every 14 days for 6 cycles) |