A Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin With Radiation Therapy Followed by Pemetrexed in Patients With Inoperable Non-Small-Cell Lung Cancer

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the 2-year survival rate of both of the chemotherapy regimens in patients with inoperable non-small-cell lung cancer.

Official Title
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Phase 1/2 Study of Pemetrexed (Alimta) Plus Carboplatin, or Pemetrexed Plus Cisplatin With Concurrent Radiation Therapy Followed by Every-21-Day Pemetrexed Consolidation in Patients With Favorable-Prognosis Inoperable Stage IIIA/B Non-Small-Cell Lung Cancer (NSCLC)

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Drug: cisplatin
* Drug: carboplatin
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inoperable non small cell lung cancer No weight loss greater than 10% in 3 months prior to enrolling in trial Adequate kidney function Adequate liver function Adequate lung function Exclusion Criteria: Previous surgery to remove lung tumor Previous chemotherapy or radiation therapy or lung cancer Inability to take vitamin supplementation Heart attack within past 6 months Active infection

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: A: Pemetrexed + Carboplatin<br>Pemetrexed + Carboplatin | Drug: pemetrexed<br>* Phase 1 - 500 milligram/meter squared (mg/m²), administered intravenously, every 21 days for 3 cycles Phase 2 - 500 mg/m², administered intravenously, every 21 days for 3 cycles Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation therapy for each phase<br>* Other names: Alimta;Drug: carboplatin<br>* Phase 1 - dosed at area under the curve (AUC) 2 milligram/milliliter*minute (mg/mL*min), administered intravenously, Days 1, 8, 22, 29 and 43 Phase 2 - dosed at AUC 5 mg/mL*min, administered intravenously, every 21 days for 3 cycles<br>Radiation: radiation therapy<br>* Phase 1 - 2 Gray, daily, 5 days a week for Days 1-51 Phase 2 - 2 Gray, daily, 5 days a week for Days 1-45<br>|
| Experimental: B: Pemetrexed + Cisplatin<br>Pemetrexed + Cisplatin | Drug: pemetrexed<br>* Phase 1 - 500 milligram/meter squared (mg/m²), administered intravenously, every 21 days for 3 cycles Phase 2 - 500 mg/m², administered intravenously, every 21 days for 3 cycles Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation therapy for each phase<br>* Other names: Alimta;Drug: cisplatin<br>* Phase 1 - 30 mg/m² and 75 mg/m², administered intravenously, Days 1, 8, 22, 29 and 43 Phase 2 - 75 mg/m², administered intravenously, every 21 days for 3 cycles<br>Radiation: radiation therapy<br>* Phase 1 - 2 Gray, daily, 5 days a week for Days 1-51 Phase 2 - 2 Gray, daily, 5 days a week for Days 1-45<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 Carboplatin | MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) lasting >7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). | Phase 1 enrollment to the end of study treatment up to Week 11 | 
| Phase 1 - Maximum Tolerated Dose (MTD) of Cisplatin | MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) lasting >7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). | Phase 1 enrollment to the end of study treatment up to Week 11 | 
| Phase 2 - Survival Probability at 2 Years |  | Phase 2 randomization up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) | Phase 1 pharmacology toxicity was defined as the number of participants experiencing dose limiting toxicities (DLTs). DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) >7 days, febrile neutropenia, ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations), and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). Grade 5 events are the events leading to the death. | Phase 1 enrollment up to Week 11 | 
| Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. | Phase 1 enrollment to the end of the study treatment up to Week 11 | 
| Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events | Phase 2 pharmacology toxicity was defined as the number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Events section. | Phase 2 randomization to the end of the study treatment up to 30.0 months | 
| Phase 2 - Time to Progression | Time to disease progression was measured from randomization of Study Phase 2 to the first observation of disease progression according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Disease progression is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. | Phase 2 randomization to measured disease progression up to 24 months | 
| Phase 2 - Median Survival |  | Phase 2 randomization to death as the result of any cause up to 30.0 month | 
| Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. | Phase 2 randomization to the end of the treatment up to 30.0 months |