Chemotherapy and Radiation in Treating Participants With Stage 3 Non-Small Cell Lung Cancer (PROCLAIM)
|Non Small Cell Lung Cancer||Drug: Pemetrexed Drug: Cisplatin Drug: Etoposide Drug: Vinorelbine Drug: Paclitaxel Drug: Carboplatin Radiation: Thoracic Radiation Therapy (TRT)||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Overall Survival [ Time Frame: Baseline to Date of Death from Any Cause (Up to 71.4 Months) ]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.
- Progression-free Survival (PFS) [ Time Frame: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 66.6 Months) ]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.
- Objective Response Rate (Complete Response [CR] + Partial Response [PR]) [ Time Frame: Baseline to Measured Progressive Disease (Up to 7 Months) ]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.
- Survival Rates at 1, 2, and 3 Years [ Time Frame: Baseline to Date of Death from Any Cause (Up to 71.4 Months) ]The probability that survival time is at least 1, 2, or 3 years was summarized using Kaplan-Meier estimates.
- First Site of Disease Failure in Terms of Relapse [ Time Frame: Baseline to Relapse (Up to 66.6 Months) ]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.
- Percentage of Participants With a Post Baseline Swallowing Diary Score >=4 [ Time Frame: Baseline through 30 Days Post Study ]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.
- Adverse Events: The Number of Deaths Per Treatment Group [ Time Frame: Baseline through 30 Days Post Study ]The number of deaths that occurred while on study drug, the number of deaths due to adverse events (AEs) while on study drug, and the number of deaths due to the study disease (that is, disease progression) while on study drug are presented. In addition, the number of deaths within 30 days of treatment discontinuation, the number of deaths due to AEs within 30 days of treatment discontinuation, and the number of deaths due to study disease within 30 days of treatment discontinuation are presented. For both the deaths due to AEs that occurred on study and for deaths due to AEs that occurred within 30 days of treatment discontinuation, the causality (events assess as possibly related [poss related] to study drug per investigator judgement) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
|Study Start Date:||September 2008|
|Study Completion Date:||November 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm A: Pemetrexed + Cisplatin and TRT
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
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.
Pemetrexed: 500 mg/m^2, IV on Day 1 of each 21-day cycle up to 4 cycles
infusion over 10 minutes
Other Names:Drug: Cisplatin
infusion over 60 minutes with adequate anti-emetic treatment and appropriate hydration per local practice guidelinesRadiation: Thoracic Radiation Therapy (TRT)
Active Comparator: Arm B: Etoposide + Cisplatin and TRT
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
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
infusion over 60 minutes with adequate anti-emetic treatment and appropriate hydration per local practice guidelinesDrug: Etoposide
administered per local practice guidelines over a minimum of 30 minutesDrug: Vinorelbine
administered over 6-10 minutes infusion per local practice guidelinesDrug: Paclitaxel
administered as a 3-hour infusionDrug: Carboplatin
administered per local practice guidelines over 30 minutesRadiation: Thoracic Radiation Therapy (TRT)
Please refer to this study by its ClinicalTrials.gov identifier: NCT00686959
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|Study Director:||Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)||Eli Lilly and Company|