Trial Outcomes & Findings for 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 (NCT NCT00482014)
NCT ID: NCT00482014
Last Updated: 2012-11-27
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
120 participants
Primary outcome timeframe
Phase 1 enrollment to the end of study treatment up to Week 11
Results posted on
2012-11-27
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
13
|
46
|
52
|
|
Overall Study
COMPLETED
|
2
|
7
|
35
|
29
|
|
Overall Study
NOT COMPLETED
|
7
|
6
|
11
|
23
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
3
|
4
|
|
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
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Pemetrexed + Carboplatin (Study Phase 1)
n=9 Participants
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.
|
Pemetrexed + Cisplatin (Study Phase 1)
n=13 Participants
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.
|
Pemetrexed + Carboplatin (Study Phase 2)
n=46 Participants
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.
|
Pemetrexed + Cisplatin (Study Phase 2)
n=52 Participants
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.
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
61.9 Years
STANDARD_DEVIATION 8.70 • n=93 Participants
|
61.0 Years
STANDARD_DEVIATION 11.66 • n=4 Participants
|
63.6 Years
STANDARD_DEVIATION 9.92 • n=27 Participants
|
64.1 Years
STANDARD_DEVIATION 9.44 • n=483 Participants
|
63.4 Years
STANDARD_DEVIATION 9.77 • n=36 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
21 Participants
n=483 Participants
|
43 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
30 Participants
n=27 Participants
|
31 Participants
n=483 Participants
|
77 Participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
8 participants
73.3 • n=93 Participants
|
7 participants
n=4 Participants
|
36 participants
n=27 Participants
|
37 participants
n=483 Participants
|
88 participants
n=36 Participants
|
|
Race/Ethnicity, Customized
African
|
1 participants
11.7 • n=93 Participants
|
3 participants
n=4 Participants
|
5 participants
n=27 Participants
|
5 participants
n=483 Participants
|
14 participants
n=36 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 participants
1.7 • n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
0 participants
n=483 Participants
|
2 participants
n=36 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
0 participants
1.7 • n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
1 participants
n=483 Participants
|
2 participants
n=36 Participants
|
|
Race/Ethnicity, Customized
West Asian (Indian sub continent
|
0 participants
11.7 • n=93 Participants
|
2 participants
n=4 Participants
|
3 participants
n=27 Participants
|
9 participants
n=483 Participants
|
14 participants
n=36 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=93 Participants
|
13 participants
n=4 Participants
|
43 participants
n=27 Participants
|
43 participants
n=483 Participants
|
108 participants
n=36 Participants
|
|
Region of Enrollment
India
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
3 participants
n=27 Participants
|
9 participants
n=483 Participants
|
12 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: Phase 1 enrollment to the end of study treatment up to Week 11Population: All participants who were enrolled in Study Phase 1 and completed at least 6 weeks of pemetrexed + carboplatin treatment.
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).
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=9 Participants
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.
|
Pemetrexed + Cisplatin Treatment
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.
|
|---|---|---|
|
Phase 1 - Maximum Tolerated Dose (MTD) of Carboplatin
|
NA milligram/milliliter*minute (mg/mL*min)
MTD was not reached because 2 DLTs threshold wasn't reached.
|
—
|
PRIMARY outcome
Timeframe: Phase 1 enrollment to the end of study treatment up to Week 11Population: All participants who were enrolled in Study Phase 1 and completed at least 6 weeks of pemetrexed + cisplatin treatment.
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).
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=13 Participants
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.
|
Pemetrexed + Cisplatin Treatment
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.
|
|---|---|---|
|
Phase 1 - Maximum Tolerated Dose (MTD) of Cisplatin
|
NA milligrams/meter squared (mg/m²)
MTD was not reached because 2 DLTs threshold wasn't reached.
|
—
|
PRIMARY outcome
Timeframe: Phase 2 randomization up to 2 yearsPopulation: All randomized participants in Study Phase 2.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=46 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=52 Participants
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.
|
|---|---|---|
|
Phase 2 - Survival Probability at 2 Years
|
45.4 percentage survival
Interval 29.5 to 60.0
|
58.4 percentage survival
Interval 42.6 to 71.3
|
SECONDARY outcome
Timeframe: Phase 1 enrollment up to Week 11Population: All participants who were enrolled in Study Phase 1 and received at least 1 dose of study drug and 1 dose of radiation therapy.
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.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=9 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=11 Participants
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.
|
|---|---|---|
|
Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs)
Grade 5 Hemoptysis (pemetrexed+Cisplatin30 mg/m² )
|
0 participants
|
1 participants
|
|
Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs)
Grade 5 Pneumocystis jiroveci pneumonia
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Phase 1 enrollment to the end of the study treatment up to Week 11Population: All participants who were enrolled in Study Phase 1 and received at least 1 dose of study drug and 1 dose of radiation therapy.
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.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=9 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=11 Participants
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.
|
|---|---|---|
|
Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate)
Complete Response (CR)
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
|
Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate)
Partial Response (PR)
|
11.1 percentage of participants
Interval 0.28 to 48.25
|
45.5 percentage of participants
Interval 16.75 to 76.62
|
SECONDARY outcome
Timeframe: Phase 2 randomization to the end of the study treatment up to 30.0 monthsPopulation: All randomized participants who received at least 1 dose of study drug or 1 dose of radiation therapy (RT) during Study Phase 2.
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.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=46 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=52 Participants
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.
|
|---|---|---|
|
Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events
Serious Adverse Events
|
21 participants
Interval 6.0 to 12.6
|
19 participants
Interval 8.3 to
|
|
Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events
Other Nonserious Adverse Events
|
44 participants
|
51 participants
|
SECONDARY outcome
Timeframe: Phase 2 randomization to measured disease progression up to 24 monthsPopulation: All randomized participants in Study Phase 2.
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.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=46 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=52 Participants
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.
|
|---|---|---|
|
Phase 2 - Time to Progression
|
8.8 months
Interval 6.0 to 12.6
|
13.1 months
Interval 8.3 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Phase 2 randomization to death as the result of any cause up to 30.0 monthPopulation: All randomized participants in Study Phase 2.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=46 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=52 Participants
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.
|
|---|---|---|
|
Phase 2 - Median Survival
|
18.7 months
Interval 12.9 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
27.0 months
Interval 23.2 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Phase 2 randomization to the end of the treatment up to 30.0 monthsPopulation: All randomization participants in Study Phase 2.
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.
Outcome measures
| Measure |
Pemetrexed + Carboplatin Treatment Group
n=46 Participants
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.
|
Pemetrexed + Cisplatin Treatment
n=52 Participants
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.
|
|---|---|---|
|
Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate)
Complete Response (CR)
|
6.5 percentage of participants
Interval 1.4 to 17.9
|
3.8 percentage of participants
Interval 0.5 to 13.2
|
|
Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate)
Partial Response (PR)
|
45.7 percentage of participants
Interval 30.9 to 61.0
|
42.3 percentage of participants
Interval 28.7 to 56.8
|
Adverse Events
Phase 1: Pemetrexed + Carboplatin
Serious events: 6 serious events
Other events: 9 other events
Deaths: 0 deaths
Phase 1: Pemetrexed + Cisplatin
Serious events: 5 serious events
Other events: 10 other events
Deaths: 0 deaths
Phase 2: Pemetrexed + Carboplatin
Serious events: 21 serious events
Other events: 44 other events
Deaths: 0 deaths
Phase 2: Pemetrexed + Cisplatin
Serious events: 19 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: Pemetrexed + Carboplatin
n=9 participants at risk
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.
|
Phase 1: Pemetrexed + Cisplatin
n=13 participants at risk
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 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 + Cis + RT) therapy.
|
Phase 2: Pemetrexed + Carboplatin
n=46 participants at risk
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.
|
Phase 2: Pemetrexed + Cisplatin
n=52 participants at risk
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.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
0.00%
0/52
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
2.2%
1/46 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
4.3%
2/46 • Number of events 2
|
0.00%
0/52
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
5.8%
3/52 • Number of events 3
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
3.8%
2/52 • Number of events 2
|
|
Cardiac disorders
Oedema peripheral
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 2
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 4
|
0.00%
0/52
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 4
|
3.8%
2/52 • Number of events 2
|
|
General disorders
Asthenia
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
General disorders
Chest pain
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
General disorders
Death
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
|
General disorders
General physical health deterioration
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/9
|
15.4%
2/13 • Number of events 2
|
4.3%
2/46 • Number of events 2
|
0.00%
0/52
|
|
Infections and infestations
Cellulitis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
3.8%
2/52 • Number of events 2
|
|
Infections and infestations
Dysentery
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Infections and infestations
Herpes oesophagitis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Infections and infestations
Localised infection
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Infections and infestations
Lung infection
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Infections and infestations
Mediastinitis
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
|
Infections and infestations
Oesophageal candidiasis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Infections and infestations
Pneumonia
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
4.3%
2/46 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
|
Infections and infestations
Pseudomembranous colitis
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Injury, poisoning and procedural complications
Radiation oesophagitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
3.8%
2/52 • Number of events 3
|
|
Injury, poisoning and procedural complications
Radiation pneumonitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/9
|
7.7%
1/13 • Number of events 2
|
0.00%
0/46
|
0.00%
0/52
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/9
|
0.00%
0/13
|
10.9%
5/46 • Number of events 5
|
9.6%
5/52 • Number of events 8
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Cerebral infarction
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Convulsion
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 2
|
0.00%
0/52
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
0.00%
0/52
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Nervous system disorders
Syncope
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopleural fistula
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
4.3%
2/46 • Number of events 2
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Surgical and medical procedures
Thoracotomy
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Vascular disorders
Hypotension
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
9.6%
5/52 • Number of events 7
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Vascular disorders
Pulmonary embolism
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
7.7%
4/52 • Number of events 4
|
Other adverse events
| Measure |
Phase 1: Pemetrexed + Carboplatin
n=9 participants at risk
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.
|
Phase 1: Pemetrexed + Cisplatin
n=13 participants at risk
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 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 + Cis + RT) therapy.
|
Phase 2: Pemetrexed + Carboplatin
n=46 participants at risk
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.
|
Phase 2: Pemetrexed + Cisplatin
n=52 participants at risk
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.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
44.4%
4/9 • Number of events 4
|
38.5%
5/13 • Number of events 6
|
30.4%
14/46 • Number of events 24
|
30.8%
16/52 • Number of events 23
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.1%
1/9 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
10.9%
5/46 • Number of events 6
|
3.8%
2/52 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 5
|
5.8%
3/52 • Number of events 3
|
|
Blood and lymphatic system disorders
Neutropenia
|
22.2%
2/9 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
34.8%
16/46 • Number of events 27
|
23.1%
12/52 • Number of events 15
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Blood and lymphatic system disorders
Thrombocythaemia
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.1%
1/9 • Number of events 1
|
15.4%
2/13 • Number of events 2
|
8.7%
4/46 • Number of events 8
|
9.6%
5/52 • Number of events 7
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Cardiac disorders
Oedema peripheral
|
0.00%
0/9
|
7.7%
1/13 • Number of events 2
|
8.7%
4/46 • Number of events 6
|
3.8%
2/52 • Number of events 2
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Eye disorders
Vision blurred
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Gastrointestinal disorders
Constipation
|
22.2%
2/9 • Number of events 2
|
30.8%
4/13 • Number of events 6
|
30.4%
14/46 • Number of events 17
|
28.8%
15/52 • Number of events 16
|
|
Gastrointestinal disorders
Diarrhoea
|
22.2%
2/9 • Number of events 2
|
23.1%
3/13 • Number of events 3
|
10.9%
5/46 • Number of events 7
|
19.2%
10/52 • Number of events 10
|
|
Gastrointestinal disorders
Dry mouth
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
|
Gastrointestinal disorders
Dyspepsia
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
15.2%
7/46 • Number of events 8
|
13.5%
7/52 • Number of events 8
|
|
Gastrointestinal disorders
Dysphagia
|
66.7%
6/9 • Number of events 8
|
38.5%
5/13 • Number of events 5
|
41.3%
19/46 • Number of events 20
|
34.6%
18/52 • Number of events 25
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Gastrointestinal disorders
Nausea
|
44.4%
4/9 • Number of events 5
|
38.5%
5/13 • Number of events 7
|
45.7%
21/46 • Number of events 24
|
53.8%
28/52 • Number of events 40
|
|
Gastrointestinal disorders
Oesophagitis
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
41.3%
19/46 • Number of events 23
|
40.4%
21/52 • Number of events 26
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
3/9 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
4.3%
2/46 • Number of events 2
|
5.8%
3/52 • Number of events 4
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9 • Number of events 2
|
15.4%
2/13 • Number of events 3
|
17.4%
8/46 • Number of events 13
|
32.7%
17/52 • Number of events 24
|
|
General disorders
Asthenia
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 4
|
13.5%
7/52 • Number of events 8
|
|
General disorders
Breakthrough pain
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
General disorders
Chest pain
|
0.00%
0/9
|
0.00%
0/13
|
15.2%
7/46 • Number of events 7
|
13.5%
7/52 • Number of events 11
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
6.5%
3/46 • Number of events 6
|
0.00%
0/52
|
|
General disorders
Fatigue
|
66.7%
6/9 • Number of events 7
|
53.8%
7/13 • Number of events 8
|
56.5%
26/46 • Number of events 32
|
51.9%
27/52 • Number of events 36
|
|
General disorders
Mucosal inflammation
|
0.00%
0/9
|
0.00%
0/13
|
13.0%
6/46 • Number of events 6
|
11.5%
6/52 • Number of events 6
|
|
General disorders
Oedema
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
General disorders
Pain
|
0.00%
0/9
|
15.4%
2/13 • Number of events 2
|
0.00%
0/46
|
5.8%
3/52 • Number of events 4
|
|
General disorders
Pyrexia
|
33.3%
3/9 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
8.7%
4/46 • Number of events 6
|
9.6%
5/52 • Number of events 5
|
|
Hepatobiliary disorders
Hypoalbuminaemia
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
7.7%
4/52 • Number of events 6
|
|
Infections and infestations
Bronchitis
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 5
|
3.8%
2/52 • Number of events 2
|
|
Infections and infestations
Candidiasis
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
7.7%
4/52 • Number of events 5
|
|
Infections and infestations
Localised infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
7.7%
4/52 • Number of events 4
|
|
Infections and infestations
Pneumonia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/9
|
0.00%
0/13
|
10.9%
5/46 • Number of events 6
|
5.8%
3/52 • Number of events 3
|
|
Infections and infestations
Urinary tract infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
5.8%
3/52 • Number of events 3
|
|
Injury, poisoning and procedural complications
Radiation oesophagitis
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
2.2%
1/46 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
0.00%
0/9
|
7.7%
1/13 • Number of events 3
|
10.9%
5/46 • Number of events 5
|
5.8%
3/52 • Number of events 3
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Investigations
Blood creatinine
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
5.8%
3/52 • Number of events 4
|
|
Investigations
Blood lactate dehydrogenase
|
0.00%
0/9
|
7.7%
1/13 • Number of events 2
|
0.00%
0/46
|
0.00%
0/52
|
|
Investigations
Creatinine renal clearance decreased
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
5.8%
3/52 • Number of events 3
|
|
Investigations
Gamma-glutamyltransferase increased
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Investigations
Haemoglobin
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
0.00%
0/52
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/9
|
0.00%
0/13
|
17.4%
8/46 • Number of events 12
|
7.7%
4/52 • Number of events 7
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 6
|
5.8%
3/52 • Number of events 4
|
|
Investigations
Platelet count decreased
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 9
|
5.8%
3/52 • Number of events 4
|
|
Investigations
Weight decreased
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
28.3%
13/46 • Number of events 13
|
17.3%
9/52 • Number of events 9
|
|
Investigations
White blood cell count decreased
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
5.8%
3/52 • Number of events 4
|
|
Metabolism and nutrition disorders
Anorexia
|
22.2%
2/9 • Number of events 3
|
23.1%
3/13 • Number of events 3
|
26.1%
12/46 • Number of events 12
|
17.3%
9/52 • Number of events 9
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/9
|
15.4%
2/13 • Number of events 3
|
4.3%
2/46 • Number of events 2
|
5.8%
3/52 • Number of events 4
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
21.7%
10/46 • Number of events 10
|
15.4%
8/52 • Number of events 8
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/9
|
0.00%
0/13
|
10.9%
5/46 • Number of events 5
|
11.5%
6/52 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/9
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
5.8%
3/52 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
11.5%
6/52 • Number of events 13
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/9
|
15.4%
2/13 • Number of events 2
|
21.7%
10/46 • Number of events 16
|
15.4%
8/52 • Number of events 12
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 7
|
15.4%
8/52 • Number of events 13
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/9
|
0.00%
0/13
|
8.7%
4/46 • Number of events 4
|
3.8%
2/52 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/9
|
15.4%
2/13 • Number of events 2
|
10.9%
5/46 • Number of events 5
|
9.6%
5/52 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
8.7%
4/46 • Number of events 4
|
3.8%
2/52 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
5.8%
3/52 • Number of events 3
|
|
Nervous system disorders
Ageusia
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Dizziness
|
22.2%
2/9 • Number of events 2
|
15.4%
2/13 • Number of events 2
|
19.6%
9/46 • Number of events 10
|
7.7%
4/52 • Number of events 7
|
|
Nervous system disorders
Dysgeusia
|
44.4%
4/9 • Number of events 4
|
7.7%
1/13 • Number of events 1
|
10.9%
5/46 • Number of events 5
|
9.6%
5/52 • Number of events 6
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
10.9%
5/46 • Number of events 5
|
7.7%
4/52 • Number of events 4
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Peripheral motor neuropathy
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
22.2%
2/9 • Number of events 2
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
1.9%
1/52 • Number of events 1
|
|
Nervous system disorders
Restless legs syndrome
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Nervous system disorders
Tremor
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Psychiatric disorders
Anxiety
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
13.0%
6/46 • Number of events 6
|
11.5%
6/52 • Number of events 6
|
|
Psychiatric disorders
Depression
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
13.0%
6/46 • Number of events 7
|
11.5%
6/52 • Number of events 6
|
|
Psychiatric disorders
Insomnia
|
33.3%
3/9 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
23.9%
11/46 • Number of events 11
|
17.3%
9/52 • Number of events 9
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
2.2%
1/46 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
2.2%
1/46 • Number of events 1
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.2%
2/9 • Number of events 2
|
15.4%
2/13 • Number of events 3
|
32.6%
15/46 • Number of events 15
|
26.9%
14/52 • Number of events 16
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
11.1%
1/9 • Number of events 1
|
15.4%
2/13 • Number of events 2
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
3/9 • Number of events 3
|
30.8%
4/13 • Number of events 5
|
19.6%
9/46 • Number of events 10
|
23.1%
12/52 • Number of events 13
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/9
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
9.6%
5/52 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
2.2%
1/46 • Number of events 1
|
7.7%
4/52 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
6.5%
3/46 • Number of events 4
|
13.5%
7/52 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
2.2%
1/46 • Number of events 1
|
1.9%
1/52 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
4.3%
2/46 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/9
|
15.4%
2/13 • Number of events 2
|
4.3%
2/46 • Number of events 2
|
5.8%
3/52 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
3.8%
2/52 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
22.2%
2/9 • Number of events 3
|
0.00%
0/13
|
0.00%
0/46
|
1.9%
1/52 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
4.3%
2/46 • Number of events 2
|
3.8%
2/52 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.1%
1/9 • Number of events 1
|
0.00%
0/13
|
0.00%
0/46
|
0.00%
0/52
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
3/9 • Number of events 3
|
15.4%
2/13 • Number of events 2
|
6.5%
3/46 • Number of events 3
|
7.7%
4/52 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/9
|
7.7%
1/13 • Number of events 1
|
0.00%
0/46
|
0.00%
0/52
|
|
Vascular disorders
Hypertension
|
0.00%
0/9
|
0.00%
0/13
|
6.5%
3/46 • Number of events 3
|
1.9%
1/52 • Number of events 1
|
|
Vascular disorders
Hypotension
|
11.1%
1/9 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
6.5%
3/46 • Number of events 3
|
7.7%
4/52 • Number of events 5
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/9
|
0.00%
0/13
|
0.00%
0/46
|
5.8%
3/52 • Number of events 3
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60