Chemotherapy and Radiation in Treating Participants With Stage 3 Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study will compare the overall survival of participants with locally-advanced, Stage III Non-Small Cell Lung Cancer (NSCLC) with nonsquamous cell histology.

Official Title
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Phase 3 Study of Pemetrexed, Cisplatin, and Radiotherapy Followed by Consolidation Pemetrexed Versus Etoposide, Cisplatin, and Radiotherapy Followed by Consolidation Cytotoxic Chemotherapy of Choice in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer Other Than Predominantly Squamous Cell Histology

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Etoposide
* Drug: Vinorelbine
* Drug: Paclitaxel
* Drug: Carboplatin
* Radiation: Thoracic Radiation Therapy (TRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have Stage IIIA or IIIIB NSCLC of the non-squamous type Participants must have measureable tumor lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated on computerized tomography (CT) scan Participants must be physically mobile, take care of themselves and must be up and about and able to perform light activities, such as light housework or office work Participants must be 18 years of age or older Participants must have lost no more than 10% of their body weight in the previous 3 months Women must be sterile, postmenopausal, or on contraception, and men must be sterile or on contraception Participants' test results assessing the function of their blood forming tissue, kidneys, liver, and lungs must be satisfactory Participants with Stage IIIB NSCLC who have supraclavicular nodal involvement may be entered into this study. However, participants with cervical nodes are not permitted. The upper border of supraclavicular nodes must not extend above the upper border of the lateral end of the clavicle, extended medially. Exclusion Criteria: Participants cannot have other on-going (uncontrolled) illnesses, including active infections, recent heart problems, or psychiatric illnesses Participants who are unable to take vitamins (including injections of vitamin B12) or oral cortisone medication Participants who have had a heart attack (myocardial infarction) or other cardiac issues within 6 months of the trial Participants who have received other investigational drugs within the last 30 days Participants who are unable to stop taking more than 1.3 grams of aspirin on a daily basis or non-steroidal anti-inflammatory agents Participants who have diseases considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumors Participants who had prior thoracic radiation. However, other prior radiotherapy is allowed. Participants must have recovered from the toxic effects of the treatment prior to study enrollment. Participants may not have received whole pelvis radiation or radiation to more than 25% of their bone marrow. Prior radiotherapy must have been completed at least 30 days prior to study treatment. Participants who have a radiation treatment plan that would expose more than 35% of the volume of their lung to 20 gray (Gy) or more of radiation Participants who have concurrent cancer from another primary site requiring treatment of any kind within the past 5 years. Exemptions to this will be permitted on a case-by-case basis after prior approval by the Sponsor physician or designate if the investigator believes the participant's risk of recurrence and death is very low. Curatively treated nonmelanoma skin cancer or in situ carcinoma of any origin is allowed. Participants with recurrence of a previously resected lung cancer or who have a second primary lung cancer are ineligible.

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 |
| --- | --- |
| Experimental: Arm A: Pemetrexed + Cisplatin and TRT<br>Participants were treated with Pemetrexed plus Cisplatin and concurrent thoracic radiation therapy (TRT) (Concurrent Phase) for three 21-day cycles, followed by a 3-5 week Recovery Period, then treated with consolidation chemotherapy with pemetrexed (Consolidation Phase) for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 milligrams per meter squared (mg/m^2), intravenous (IV) on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray [Gy] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m^2, IV on Day 1 of each 21-day cycle up to 4 cycles | Drug: Pemetrexed<br>* infusion over 10 minutes<br>* Other names: LY231514;Drug: Cisplatin<br>* infusion over 60 minutes with adequate anti-emetic treatment and appropriate hydration per local practice guidelines<br>Radiation: Thoracic Radiation Therapy (TRT)<br> <br> |
| Active Comparator: Arm B: Etoposide + Cisplatin and TRT<br>Participants were treated with Etoposide plus Cisplatin and concurrent TRT (Concurrent Phase) for two 28-day cycles, followed by a 3-5 week Recovery Period, then received consolidation treatment with cytotoxic chemotherapy of choice (Consolidation Phase) for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22 | Drug: Cisplatin<br>* infusion over 60 minutes with adequate anti-emetic treatment and appropriate hydration per local practice guidelines<br>Drug: Etoposide<br>* administered per local practice guidelines over a minimum of 30 minutes<br>Drug: Vinorelbine<br>* administered over 6-10 minutes infusion per local practice guidelines<br>Drug: Paclitaxel<br>* administered as a 3-hour infusion<br>Drug: Carboplatin<br>* administered per local practice guidelines over 30 minutes<br>Radiation: Thoracic Radiation Therapy (TRT)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival (OS) time is from baseline to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates. | Baseline to Date of Death from Any Cause (Up to 71.4 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free survival (PFS) time is from baseline to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have died or to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates. | Baseline to Measured Progressive Disease or Death from Any Cause (Up to 66.6 Months) | 
| Objective Response Rate (Complete Response [CR] + Partial Response [PR]) | Overall response rate (ORR) is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. | Baseline to Measured Progressive Disease (Up to 7 Months) | 
| Survival Rates at 1, 2, and 3 Years | The probability that survival time is at least 1, 2, or 3 years was summarized using Kaplan-Meier estimates. | Baseline to Date of Death from Any Cause (Up to 71.4 Months) | 
| First Site of Disease Failure in Terms of Relapse | The percentage of participants with first sites of disease failure in terms of relapse within the radiation treatment field, inside the thorax, (outside of the radiation field), or distant disease are presented. Results were summarized using Kaplan-Meier estimates. Some participants relapsed in more than 1 location/site and appear in more than a single category. | Baseline to Relapse (Up to 66.6 Months) | 
| Percentage of Participants With a Post Baseline Swallowing Diary Score >=4 | Participants were provided with a swallowing diary to record issues with swallowing using a 5-point categorical scale: (1) no problems; (2) mild soreness; (3) swallowing solids with some difficulty; (4) inability to swallow solids; and (5) inability to swallow liquids. Participants rated swallowing over the previous 24 hours. The percentage of participants was calculated by dividing the number of with a post baseline swallowing diary score >=4 by total number of participants analyzed, multiplied by 100. No adjustments were made for the number of available assessments nor were any interpolation of missing assessments made. | Baseline through 30 Days Post Study |