A Study of Pemetrexed/Cisplatin as Pre-operative Treatment of Early Stage Nonsquamous Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to assess how well the combination of pemetrexed with cisplatin can reduce tumor size.

Official Title
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An Exploratory Phase 2 Study of Pemetrexed/Cisplatin as Pre-operative Chemotherapy in the Treatment of Stage IIIAN2 Nonsquamous Non-Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Folic Acid
* Drug: Vitamin B12
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nonsquamous Non-Small Cell Lung Cancer that was confirmed by tissue biopsy Stage IIIAN2 disease (T1aN2, T1bN2, T2aN2, T2bN2, and T3N2) Tumor considered potentially resectable Good performance status (score of 0 or 1) according to Eastern Cooperative Oncology Group scale (ECOG) No prior therapy for lung cancer Measurable disease according to version 1.1 of Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Life expectancy of at least 6 months Organs are functioning well (bone marrow reserve, liver, kidney, lung) Signed Informed Consent Women must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen (for example, intrauterine device, birth control pills, or barrier device) during and for 6 months after last dose of study drug; must have a negative pregnancy test within 7 days before study enrollment; and must not be breast-feeding. Men must be surgically sterile, or compliant with a contraceptive regimen during and for 6 months after last dose of study drug. Be fit for surgery at the time of enrollment Exclusion Criteria: Receiving or have received an investigational drug or device within the last 30 days Have previously completed or withdrawn from this study or any other study investigating pemetrexed Serious concomitant systemic disorder Serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease Receiving concurrent administration of any other anticancer therapy Have received a recent (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination Inability or unwillingness to take Pemetrexed supplementation/premedication (folic acid, vitamin B12, or corticosteroids) Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day

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: Pemetrexed + Cisplatin<br> | Drug: Pemetrexed<br>* 500 milligram per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles<br>* Other names: LY231514;Drug: Cisplatin<br>* 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles<br>Drug: Folic Acid<br>* Administered orally.<br>Drug: Vitamin B12<br>* Administered Intramuscular injection.<br>Drug: Dexamethasone<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size [<10 millimeter (mm) short axis]. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100. | From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With No Viable Tumor Cells in Resected Lung Tissue [Pathological Complete Remission (pCR)] | pCR after the participant has undergone surgery was calculated as: (total number of participants with pCR) divided by (the total number of participants in pathological response population) multiplied by 100. | At the time of surgery (within 3 to 6 weeks of Day 1 of Cycle 3 [21-day cycles] of chemotherapy) | 
| Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0 | Tumor downstaging compared to baseline (Stage IIIAN2) were those participants who exhibited a downward shift in tumor extent from Stage IIIAN2 to Stages IIIA, II, I, or 0 were reported. Downstaging was based on radiological examination. Stage IIIAN2 was locally advanced and/or involved lymph nodes, metastasis in ipsilateral mediastinal and or subcarinal lymph nodes, tumors were ≤2 centimeters (cm) up to 5 cm in greatest dimension; Stage IIIA was locally advanced and/or involved lymph nodes, tumor extension was restricted to the affected lung; Stage II was locally advanced and/or involved lymph nodes; Stage I was small localized cancers, usually curable; Stage 0 the cancer did not spread beyond the inner lining of the lung. Missing responses were also reported. Percentage of participants calculated as: (number of participants with a downward shift in extent of their tumor) divided by (total number of evaluable participants) multiplied by 100. | From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapy | 
| Overall Survival (OS) | OS was defined as duration from the date of study enrollment to the date of death from any cause. Participants not known to have died as of the data inclusion cut-off date were censored at the date of last contact. The last contact for participants in post-discontinuation was the last date participant was known to be alive. | Enrollment until the date of death from any cause up to 64 months | 
| Progression-Free Survival (PFS) | PFS was defined as the time from date of first dose to the first observation of disease progression or death due to any cause. For participants not known to have died or did not have objective progressive disease (PD) as of the data inclusion cut-off date, PFS was censored at the date of the last objective progression-free disease assessment. PD was defined using RECIST v1.1 criteria as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. | Enrollment until the first date of objectively determined PD or death up to 64 months |