Concurrent Pemetrexed, Cisplatin and Radiation Therapy in Patients With Stage IIIA/B Non Small Cell Lung Cancer

Study Overview
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Brief Summary
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Measure the 1 year survival of non small cell lung cancer (NSCLC) patients who are being treated with pemetrexed in combination with cisplatin and radiation.

Official Title
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A Phase I/II Study of Concurrent Pemetrexed/Cisplatin/Radiation in Stage IIIA/B Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed Phase 1
* Drug: Cisplatin Phase 1
* Procedure: Radiation Therapy
* Drug: Pemetrexed Phase 2
* Drug: Cisplatin Phase 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Some of the requirements to be in this study are: Patient must be at least 18 years old. Patient must have been diagnosed with non-small cell lung cancer. Patient must be able to visit the doctor's office once a week. Patient must have adequate blood, liver, lungs and kidney function within the requirements of this study. Female patients of child-bearing potential must test negative for pregnancy at the time of enrollment based on a serum pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug. Exclusion Criteria: Patients cannot participate in this study for any of the following reasons: Patient has previously had chemotherapy. Patient has previously had thoracic radiation therapy. Patient has received treatment within the last 30 days with a drug that has not received approval by Health Canada for any indication at the time of study entry. Female patient is pregnant or breast-feeding. Patient is unsuitable to participate in the study in the opinion of the investigator. Patient is unable or unwilling to take folic acid, vitamin B12 supplementation, or dexamethasone.

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/Cisplatin/Radiation Phase 1<br>Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m^2) IV through 500 mg/m^2 IV on Days 1 and 22; concurrent cisplatin 25 mg/m^2 IV on Days 1-3 and 22-24 for Cohorts 1-3 and cisplatin 20 mg/m^2 IV on Days 1-5 and 22-26 for Cohort 4. Participants then received 2 additional consolidation cycles repeated every 3 weeks (q3 weeks) of pemetrexed 500 mg/m^2 IV and cisplatin 75 mg/m^2 IV. | Drug: Pemetrexed Phase 1<br>* 300 mg/m^2 IV, Days 1 and 22; intermediate dose escalation level of 400 mg/m^2 IV; then 500 mg/m^2 IV, repeated every 21 days (q 21 days) x 2 cycles<br>* Other names: Alimta;Drug: Cisplatin Phase 1<br>* Cohorts 1-3: 25 mg/m^2 IV, Days 1-3 and 22-24 then 75 mg/m^2 IV, q21 days x 2 cycles Cohort 4 carried into Phase 2: 20 mg/m^2 IV, Days 1-5 and 22-26 then 75 mg/m^2 IV, q21 days x 2 cycles.<br>Procedure: Radiation Therapy<br>* Phases 1 and 2: 61-65 Gy in 33-35 fractions<br>|
| Experimental: Pemetrexed/Cisplatin/Radiation Phase 2<br>Treatment included: radiation, 61-65 Gy in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent phase pemetrexed IV bolus as determined by Phase 1 trial to be 500 mg/m^2 IV on Days 1 and 22 ; concurrent cisplatin 20 mg/m^2 IV as determined by Phase 1 trial with cycles commencing on Days 1 and 22; 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m^2 IV and cisplatin 75 mg/m^2 IV. | Procedure: Radiation Therapy<br>* Phases 1 and 2: 61-65 Gy in 33-35 fractions<br>Drug: Pemetrexed Phase 2<br>* Concurrent phase pemetrexed IV bolus as determined by Phase 1 trial to be 500 mg/m^2 IV on Days 1 and 22.<br>* Other names: Alimta;Drug: Cisplatin Phase 2<br>* Phase 2 (Cohort 4 carried over from Phase 1): 20 mg/m^2 IV, Days 1-5 and 22-26 then 75 mg/m^2 IV, q21 days x 2 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cisplatin and Radiation Therapy | Recommended Phase 2 MTD was highest dose at which no more than 1 of 6 participants experienced dose level toxicity (DLT). DLT=(1) Grade 3/4 dysphagia/esophagitis, leukopenia, thrombocytopenia, febrile neutropenia, fatigue/malaise, pneumonitis, dermatitis, persistent elevation of bilirubin/alkaline phosphatase/aspartate aminotransferase only if resulting in delay of radiotherapy >1 week, delay of pemetrexed/cisplatin Cycle 2 >2 weeks, or delay of pemetrexed/cisplatin Cycle 3 past 5 weeks after radiotherapy; (2) other Grade 3 or 4 toxicity possibly related to concurrent treatment administration. | Baseline to measured progressive disease (PD; up to 1 year) | 
| Phase 2: Percentage of Participants With Overall Survival (OS) at 1 Year | OS was defined as the time from date of enrollment to death due to any cause. | Baseline to date of death from any cause (up to 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Number of Participants With Adverse Events (AE; Toxicity) | A listing of AEs is located in the Reported Adverse Event module. | Baseline to measured PD (up to 1 year) | 
| Phase 2: Percentage of Participants With Overall Survival (OS) at 2 Years and 3 Years | OS was defined as the time from date of enrollment to death due to any cause. | Baseline and 2 years and 3 years | 
| Phase 2: Time to Progressive Disease (PD) | Time to PD was defined as the time from study enrollment to the first date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions as references the smallest sum LD recorded since treatment started or the appearance of 1 or more new lesions. Time to PD was censored at the date of death if death was due to other cause. For participants not known to have died as of the data cut-off date and who did not have PD, time to PD was censored at the last progression-free disease assessment. For participants who received subsequent cancer therapy (after discontinuation from the study therapy) before PD, time to PD was censored at the date of subsequent cancer therapy initiation. | Baseline to measured PD (up to 3 years) | 
| Phase 2: Percentage of Participants With Progression Free Survival (PFS) | The percentage of participants not known to have died as of the data cut-off date or last contact and who did not have PD. | Baseline and 1 year and 2 years and 3 years | 
| Progression Free Survival (PFS) | PFS was defined as the period from study entry until PD, death, or date of last contact. For participants not known to have died as of the data cut-off date and who did not have PD, the PFS date was censored at the last contact date (contacts considered in the determination of last progression free disease assessment). | Baseline to measured PD (up to 36 months) | 
| Phase 2: Percentage of Participants With Objective Tumor Response (Response Rate) | Response using Response Evaluation Criteria In Solid Tumors (RECIST 1.0). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants with measurable disease * 100, where objective responders are those participants who have met criteria either for CR or PR. | Baseline to measured PD (up to 3 years) | 
| Phase 2: Site of Progressive Disease (PD) | Summarized participants with local (progression within the sites of initial disease)/regional (disease progression adjacent to but not within the site of initial disease at the start of treatment), distant (disease progression that is blood borne to other parts of the body, including outside the chest or involving the contralateral lung), and local + distant sites of disease. Objective PD is defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions as references the smallest sum LD recorded since treatment started or the appearance of 1 or more new lesions. | Baseline to measured PD (up to 3 years) |