Non-Small-Cell Lung Cancer
Conditions
Brief summary
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.
Interventions
DRUGpemetrexed
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
DRUGcisplatin
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
DRUGcarboplatin
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
RADIATIONradiation therapy
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
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 - Maximum Tolerated Dose (MTD) of Carboplatin | Phase 1 enrollment to the end of study treatment up to Week 11 | 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 - Maximum Tolerated Dose (MTD) of Cisplatin | Phase 1 enrollment to the end of study treatment up to Week 11 | 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 2 - Survival Probability at 2 Years | Phase 2 randomization up to 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events | Phase 2 randomization to the end of the study treatment up to 30.0 months | 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 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) | Phase 1 enrollment up to Week 11 | 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 2 - Median Survival | Phase 2 randomization to death as the result of any cause up to 30.0 month | — |
| Phase 2 - Time to Progression | Phase 2 randomization to measured disease progression up to 24 months | 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 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Phase 2 randomization to the end of the treatment up to 30.0 months | 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 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Phase 1 enrollment to the end of the study treatment up to Week 11 | 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. |
Countries
India, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed + Carboplatin (Study Phase 1) 500 milligrams/meter squared (mg/m²) pemetrexed (Pem) every 21 days for 3 cycles + Carboplatin (Carbo) dosed at area under the curve (AUC) 2 milligram/milliliter\*minute (mg/mL\*min) on Days 1, 8, 22, 29, 43 + radiation therapy (RT) 74 Grays (Gy) total dose given 2 Gy/day over 51 days.
Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation (Pem + Carbo + RT) therapy. | 9 |
| Pemetrexed + Cisplatin (Study Phase 1) 500 mg/m² pemetrexed every 21 days for 3 cycles + Cisplatin (Cis) 30 mg/m² or 75 mg/m² on Days 1, 8, 22, 29, 43 + radiation therapy 74 Gy total dose given 2 Gy/day over 51 days.
Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation (Pem + Cis + RT) therapy. | 13 |
| Pemetrexed + Carboplatin (Study Phase 2) 500 mg/m² pemetrexed every 21 days for 3 cycles + Carboplatin dosed at AUC 5 mg/mL\*min every 21 days for 3 cycles + radiation therapy 64-68 Gy total dose given 2 Gy/day over 45 days.
Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation (Pem + Carbo + RT) therapy. | 46 |
| Pemetrexed + Cisplatin (Study Phase 2) 500 mg/m² pemetrexed every 21 days for 3 cycles + Cisplatin 75 mg/m² every 21 days for 3 cycles + radiation therapy 64-68 Gy total dose given 2 Gy/day over 45 days.
Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation (Pem + Cis + RT) therapy. | 52 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 2 | 8 |
| Overall Study | Death | 1 | 2 | 1 | 4 |
| Overall Study | Lack of Efficacy | 1 | 0 | 4 | 6 |
| Overall Study | Sponsor Decision | 1 | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 3 | 4 |
Baseline characteristics
| Characteristic | Pemetrexed + Carboplatin (Study Phase 1) | Total | Pemetrexed + Cisplatin (Study Phase 2) | Pemetrexed + Carboplatin (Study Phase 2) | Pemetrexed + Cisplatin (Study Phase 1) |
|---|---|---|---|---|---|
| Age Continuous | 61.9 Years STANDARD_DEVIATION 8.7 | 63.4 Years STANDARD_DEVIATION 9.77 | 64.1 Years STANDARD_DEVIATION 9.44 | 63.6 Years STANDARD_DEVIATION 9.92 | 61.0 Years STANDARD_DEVIATION 11.66 |
| Race/Ethnicity, Customized African | 1 participants 11.7 | 14 participants | 5 participants | 5 participants | 3 participants |
| Race/Ethnicity, Customized Caucasian | 8 participants 73.3 | 88 participants | 37 participants | 36 participants | 7 participants |
| Race/Ethnicity, Customized East Asian | 0 participants 1.7 | 2 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants 1.7 | 2 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized West Asian (Indian sub continent | 0 participants 11.7 | 14 participants | 9 participants | 3 participants | 2 participants |
| Region of Enrollment India | 0 participants | 12 participants | 9 participants | 3 participants | 0 participants |
| Region of Enrollment United States | 9 participants | 108 participants | 43 participants | 43 participants | 13 participants |
| Sex: Female, Male Female | 2 Participants | 43 Participants | 21 Participants | 16 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 77 Participants | 31 Participants | 30 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 10 / 13 | 44 / 46 | 51 / 52 |
| serious Total, serious adverse events | 6 / 9 | 5 / 13 | 21 / 46 | 19 / 52 |
Outcome results
Primary
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).
Time frame: Phase 1 enrollment to the end of study treatment up to Week 11
Population: All participants who were enrolled in Study Phase 1 and completed at least 6 weeks of pemetrexed + carboplatin treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 1 - Maximum Tolerated Dose (MTD) of Carboplatin | NA milligram/milliliter*minute (mg/mL*min) |
Primary
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).
Time frame: Phase 1 enrollment to the end of study treatment up to Week 11
Population: All participants who were enrolled in Study Phase 1 and completed at least 6 weeks of pemetrexed + cisplatin treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 1 - Maximum Tolerated Dose (MTD) of Cisplatin | NA milligrams/meter squared (mg/m²) |
Primary
Phase 2 - Survival Probability at 2 Years
Time frame: Phase 2 randomization up to 2 years
Population: All randomized participants in Study Phase 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Survival Probability at 2 Years | 45.4 percentage survival |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Survival Probability at 2 Years | 58.4 percentage survival |
Secondary
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.
Time frame: Phase 1 enrollment to the end of the study treatment up to Week 11
Population: All participants who were enrolled in Study Phase 1 and received at least 1 dose of study drug and 1 dose of radiation therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Complete Response (CR) | 0 percentage of participants |
| Pemetrexed + Carboplatin Treatment Group | Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Partial Response (PR) | 11.1 percentage of participants |
| Pemetrexed + Cisplatin Treatment | Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Complete Response (CR) | 0 percentage of participants |
| Pemetrexed + Cisplatin Treatment | Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Partial Response (PR) | 45.5 percentage of participants |
Secondary
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.
Time frame: Phase 1 enrollment up to Week 11
Population: All participants who were enrolled in Study Phase 1 and received at least 1 dose of study drug and 1 dose of radiation therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) | Grade 5 Pneumocystis jiroveci pneumonia | 1 participants |
| Pemetrexed + Carboplatin Treatment Group | Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) | Grade 5 Hemoptysis (pemetrexed+Cisplatin30 mg/m² ) | 0 participants |
| Pemetrexed + Cisplatin Treatment | Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) | Grade 5 Pneumocystis jiroveci pneumonia | 0 participants |
| Pemetrexed + Cisplatin Treatment | Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) | Grade 5 Hemoptysis (pemetrexed+Cisplatin30 mg/m² ) | 1 participants |
Secondary
Phase 2 - Median Survival
Time frame: Phase 2 randomization to death as the result of any cause up to 30.0 month
Population: All randomized participants in Study Phase 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Median Survival | 18.7 months |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Median Survival | 27.0 months |
Secondary
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.
Time frame: Phase 2 randomization to the end of the treatment up to 30.0 months
Population: All randomization participants in Study Phase 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Complete Response (CR) | 6.5 percentage of participants |
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Partial Response (PR) | 45.7 percentage of participants |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Complete Response (CR) | 3.8 percentage of participants |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate) | Partial Response (PR) | 42.3 percentage of participants |
Secondary
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.
Time frame: Phase 2 randomization to the end of the study treatment up to 30.0 months
Population: All randomized participants who received at least 1 dose of study drug or 1 dose of radiation therapy (RT) during Study Phase 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events | Serious Adverse Events | 21 participants |
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events | Other Nonserious Adverse Events | 44 participants |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events | Serious Adverse Events | 19 participants |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events | Other Nonserious Adverse Events | 51 participants |
Secondary
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.
Time frame: Phase 2 randomization to measured disease progression up to 24 months
Population: All randomized participants in Study Phase 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed + Carboplatin Treatment Group | Phase 2 - Time to Progression | 8.8 months |
| Pemetrexed + Cisplatin Treatment | Phase 2 - Time to Progression | 13.1 months |