A Study for Patients With Non-Squamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Chemotherapy for patients with non-squamous non-small cell lung cancer. Patients are given folic acid, vitamin B12 and steroids, both before and during treatment, to reduce the side effects associated with pemetrexed. The aim is whether it is possible to simplify the folic acid and steroid schedule without increasing toxicity.

Official Title
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Pemetrexed With Simplified Folate and Dexamethasone Supplementation Versus Pemetrexed With Standard Supplementation as Second-line Chemotherapy for Patients With Non-squamous Non-small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Dietary Supplement: Folic acid
* Dietary Supplement: Folic Acid
* Dietary Supplement: Vitamin B12
* Drug: dexamethasone
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC) with locally advanced or metastatic disease (Stage IIIA, IIIB or IV)that is of non-squamous histology Patients must have failed only one prior chemotherapy regime and must be considered eligible for further chemotherapy following progression of their disease. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Adequate organ function Exclusion Criteria: Concurrent administration of any other anti-tumor therapy Other co-existing malignancies Pregnancy or breast feeding Serious concomitant disorders Inability or unwillingness to take folic acid or vitamin B12 supplementation

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Vitamin and Steroid Schedule + Pemetrexed<br>Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment. | Drug: pemetrexed<br>* 500 mg/m^2 intravenous infusion on day 1 of each 21-day cycle. Number of Cycles: Until progression or to a maximum of 6 cycles.<br>* Other names: LY231514;Dietary Supplement: Folic acid<br>* 350-1000 micrograms taken orally for at least 5 daily doses during the 7-day period prior to the first dose of pemetrexed then continues daily throughout treatment until 3 weeks after the last dose of pemetrexed.<br>* Other names: Folate;Dietary Supplement: Vitamin B12<br>* 1000 micrograms intramuscular injection of vitamin B12 during the week prior to the first dose of pemetrexed then further injections given approximately every 9 weeks until 3 weeks after the last dose of pemetrexed.<br>Drug: dexamethasone<br>* 4 mg taken orally [or equivalent] twice per day the day before, the day of, and the day after the first day of pemetrexed. Continue to give dexamethasone twice per day the day before, the day of, and the day after each dose of pemetrexed.<br>|
| Experimental: Simplified Vitamin and Steroid Schedule + Pemetrexed<br>Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only. | Drug: pemetrexed<br>* 500 mg/m^2 intravenous infusion on day 1 of each 21-day cycle. Number of Cycles: Until progression or to a maximum of 6 cycles.<br>* Other names: LY231514;Dietary Supplement: Folic Acid<br>* 350-1000 micrograms taken orally for two consecutive daily doses of folic acid the day before and the day of the first dose of pemetrexed the continues throughout treatment and for 3 weeks after the last dose of pemetrexed.<br>* Other names: Folate;Dietary Supplement: Vitamin B12<br>* 1000 micrograms intramuscular injection of vitamin B12 during the week prior to the first dose of pemetrexed then further injections given approximately every 9 weeks until 3 weeks after the last dose of pemetrexed.<br>Drug: dexamethasone<br>* 4 mg taken orally [or equivalent] twice per day on the day of the first dose of pemetrexed. Continue to give dexamethasone twice per day on the day of each dose of pemetrexed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity | Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A detailed list of Serious and non-serious adverse events is provided in the Reported Adverse Event section. | From first dose of treatment to last dose of treatment plus 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Best Overall Tumor Response (Response Rate) | Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=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. Best Overall Tumor Response is complete response plus partial response. | Baseline until disease progression, new therapy initiated, or death from any cause, up to 12 months after enrollment. | 
| Overall Survival | Overall survival is the duration from randomization to death. For patients who are alive, overall survival is censored at the date of last contact. | Randomization (≤4 weeks from baseline visit) to 12 months after randomization | 
| Progression-free Survival (PFS) | Defined as the time from date of first dose to the first observation of disease progression, or death due to any cause. For patients who are alive and have not progressed, PFS is censored at the date of last radiological assessment. | Randomization (≤4 weeks from baseline visit) to 12 months after randomization |