Trial Outcomes & Findings for Concurrent Pemetrexed, Cisplatin and Radiation Therapy in Patients With Stage IIIA/B Non Small Cell Lung Cancer (NCT NCT00529100)

Last Updated: 2013-07-09

Results Overview

Recommended Phase 2 MTD was highest dose at which no more than 1 of 6 participants experienced dose level toxicity (DLT). DLT=(1) Grade 3/4 dysphagia/esophagitis, leukopenia, thrombocytopenia, febrile neutropenia, fatigue/malaise, pneumonitis, dermatitis, persistent elevation of bilirubin/alkaline phosphatase/aspartate aminotransferase only if resulting in delay of radiotherapy \>1 week, delay of pemetrexed/cisplatin Cycle 2 \>2 weeks, or delay of pemetrexed/cisplatin Cycle 3 past 5 weeks after radiotherapy; (2) other Grade 3 or 4 toxicity possibly related to concurrent treatment administration.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Baseline to measured progressive disease (PD; up to 1 year)

Results posted on

2013-07-09

Participant Flow

A total of 16 participants entered Phase 1 of the study. A total of 39 participants were analyzed in Phase 2, which included data from 6 Phase 1 participants.

Participant milestones

Participant milestones
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) IV through 500 mg/m\^2 IV on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 IV on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 IV on Days 1-5 and 22-26 for Cohort 4. Participants then received 2 additional consolidation cycles (every 3 weeks \[q3 weeks\]) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV.	Pemetrexed/Cisplatin/Radiation Phase 2 Treatment included: radiation, 61-65 Gy in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed IV bolus as determined by Phase 1 trial on Days 1 and 22; concurrent cisplatin as determined by Phase 1 trial with cycles commencing on Days 1 and 22; and 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV.
Overall Study STARTED	16	33
Overall Study Received at Least 1 Dose of Study Drug	16	33
Overall Study COMPLETED	16	24
Overall Study NOT COMPLETED	0	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) IV through 500 mg/m\^2 IV on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 IV on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 IV on Days 1-5 and 22-26 for Cohort 4. Participants then received 2 additional consolidation cycles (every 3 weeks \[q3 weeks\]) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV.	Pemetrexed/Cisplatin/Radiation Phase 2 Treatment included: radiation, 61-65 Gy in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed IV bolus as determined by Phase 1 trial on Days 1 and 22; concurrent cisplatin as determined by Phase 1 trial with cycles commencing on Days 1 and 22; and 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV.
Overall Study Adverse Event	0	5
Overall Study Protocol Violation	0	1
Overall Study Progressive Disease	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study Participant Ineligibility	0	1

Baseline Characteristics

Concurrent Pemetrexed, Cisplatin and Radiation Therapy in Patients With Stage IIIA/B Non Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=10 Participants Participants were strictly in Phase 1. Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) IV through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 IV on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 IV on Days 1-5 and 22-26 for Cohort 4. Participants then received 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV.	Pemetrexed/Cisplatin/Radiation Phase 1-Phase 2 n=6 Participants Participants were overlap in Phase 1 and Phase 2.	Pemetrexed/Cisplatin/Radiation Phase 2 n=33 Participants Participants were strictly in Phase 2. Treatment included: radiation, 61-65 Gy in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed IV bolus as determined by Phase 1 trial on Days 1 and 22; concurrent cisplatin as determined by Phase 1 trial with cycles commencing on Days 1 and 22; 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m2 IV.	Total n=49 Participants Total of all reporting groups
Age Continuous	60.3 years STANDARD_DEVIATION 8.0 • n=5 Participants	64.3 years STANDARD_DEVIATION 8.1 • n=7 Participants	61.2 years STANDARD_DEVIATION 10.5 • n=5 Participants	61.4 years STANDARD_DEVIATION 9.7 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	18 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	6 Participants n=7 Participants	30 Participants n=5 Participants	46 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	5 Participants n=7 Participants	27 Participants n=5 Participants	41 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Canada	10 participants n=5 Participants	6 participants n=7 Participants	33 participants n=5 Participants	49 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to measured progressive disease (PD; up to 1 year)

Population: The treated population included all participants who received at least 1 dose of either study therapy (that is, pemetrexed, cisplatin, or radiation).

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=16 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 1: Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cisplatin and Radiation Therapy Concurrent Phase MTD: Pemetrexed	500 milligrams per square meter (mg/m^2)
Phase 1: Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cisplatin and Radiation Therapy Concurrent Phase MTD: Cisplatin	20 milligrams per square meter (mg/m^2)
Phase 1: Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cisplatin and Radiation Therapy Consolidation Phase MTD: Pemetrexed	500 milligrams per square meter (mg/m^2)
Phase 1: Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Cisplatin and Radiation Therapy Consolidation Phase MTD: Cisplatin	75 milligrams per square meter (mg/m^2)

PRIMARY outcome

Timeframe: Baseline to date of death from any cause (up to 1 year)

Population: The treated population was considered the primary analysis population for the efficacy endpoints. The efficacy analysis was also completed on the protocol-qualified (PQ)population to assess the sensitivity of the results.

OS was defined as the time from date of enrollment to death due to any cause.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=39 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 2: Percentage of Participants With Overall Survival (OS) at 1 Year	79.0 percentage of participants Interval 66.1 to 92.0

SECONDARY outcome

Timeframe: Baseline to measured PD (up to 1 year)

Population: The treated population was used for this analysis and included all participants who received at least 1 dose of either study therapy (pemetrexed, cisplatin, or radiation).

A listing of AEs is located in the Reported Adverse Event module.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=10 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 1: Number of Participants With Adverse Events (AE; Toxicity) Serious Adverse Events (SAEs)	5 participants
Phase 1: Number of Participants With Adverse Events (AE; Toxicity) Other Non-serious Adverse Events (AEs)	10 participants

SECONDARY outcome

Timeframe: Baseline and 2 years and 3 years

Population: The treated population was used for this analysis and included all participants who received at least 1 dose of either study therapy (pemetrexed, cisplatin, or radiation).

OS was defined as the time from date of enrollment to death due to any cause.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=39 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 2: Percentage of Participants With Overall Survival (OS) at 2 Years and 3 Years 3 years	46.2 percentage of participants Interval 30.5 to 61.8
Phase 2: Percentage of Participants With Overall Survival (OS) at 2 Years and 3 Years 2 years	56.4 percentage of participants Interval 40.8 to 72.0

SECONDARY outcome

Timeframe: Baseline to measured PD (up to 3 years)

Population: The treated population was used for this analysis and included all participants who received at least 1 dose of either study therapy (pemetrexed, cisplatin, or radiation). Eleven participants were censored.

Time to PD was defined as the time from study enrollment to the first date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions as references the smallest sum LD recorded since treatment started or the appearance of 1 or more new lesions. Time to PD was censored at the date of death if death was due to other cause. For participants not known to have died as of the data cut-off date and who did not have PD, time to PD was censored at the last progression-free disease assessment. For participants who received subsequent cancer therapy (after discontinuation from the study therapy) before PD, time to PD was censored at the date of subsequent cancer therapy initiation.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=39 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 2: Time to Progressive Disease (PD)	13.7 months Interval 10.2 to 19.2

SECONDARY outcome

Timeframe: Baseline and 1 year and 2 years and 3 years

Population: The treated population was used for this analysis and included all participants who received at least 1 dose of either study therapy (pemetrexed, cisplatin, or radiation).

The percentage of participants not known to have died as of the data cut-off date or last contact and who did not have PD.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=39 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 2: Percentage of Participants With Progression Free Survival (PFS) 1 Year	48.7 percentage of participants Interval 33.0 to 64.4
Phase 2: Percentage of Participants With Progression Free Survival (PFS) 2 Years	30.8 percentage of participants Interval 16.3 to 45.3
Phase 2: Percentage of Participants With Progression Free Survival (PFS) 3 Years	20.2 percentage of participants Interval 7.5 to 32.9

SECONDARY outcome

Timeframe: Baseline to measured PD (up to 36 months)

PFS was defined as the period from study entry until PD, death, or date of last contact. For participants not known to have died as of the data cut-off date and who did not have PD, the PFS date was censored at the last contact date (contacts considered in the determination of last progression free disease assessment).

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=39 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Progression Free Survival (PFS)	11.8 months Interval 9.8 to 19.2

SECONDARY outcome

Timeframe: Baseline to measured PD (up to 3 years)

Response using Response Evaluation Criteria In Solid Tumors (RECIST 1.0). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants with measurable disease \* 100, where objective responders are those participants who have met criteria either for CR or PR.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=37 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 2: Percentage of Participants With Objective Tumor Response (Response Rate) Complete Response	0 percentage of participants Interval 0.0 to 0.0
Phase 2: Percentage of Participants With Objective Tumor Response (Response Rate) Partial Response	45.95 percentage of participants Interval 29.89 to 62.0

SECONDARY outcome

Timeframe: Baseline to measured PD (up to 3 years)

Population: The treated population was used for this analysis and included all participants who received at least 1 dose of either study therapy (pemetrexed, cisplatin, or radiation) and who had PD.

Summarized participants with local (progression within the sites of initial disease)/regional (disease progression adjacent to but not within the site of initial disease at the start of treatment), distant (disease progression that is blood borne to other parts of the body, including outside the chest or involving the contralateral lung), and local + distant sites of disease. Objective PD is defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) as at least a 20% increase in the sum of the longest diameter (LD) of target lesions as references the smallest sum LD recorded since treatment started or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=27 Participants Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on days 1-5 and 22-26 for cohort four. Participants then received two additional consolidation cycles (q3 weekly) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Phase 2: Site of Progressive Disease (PD) Local/Regional	8 participants
Phase 2: Site of Progressive Disease (PD) Distant	17 participants
Phase 2: Site of Progressive Disease (PD) Local + Distant	1 participants
Phase 2: Site of Progressive Disease (PD) Unknown	1 participants

Adverse Events

Pemetrexed/Cisplatin/Radiation Phase 1

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Pemetrexed/Cisplatin/Radiation Phase 1-2

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Pemetrexed/Cisplatin/Radiation Phase 2

Serious events: 9 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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: LTE60

Measure	Pemetrexed/Cisplatin/Radiation Phase 1 n=10 participants at risk Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first three cohorts and cisplatin 20 mg/m\^2 on Days 1-5 and 22-26 for Cohort 4. Participants then received two additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.	Pemetrexed/Cisplatin/Radiation Phase 1-2 n=6 participants at risk Cohort 4 data from Phase (Ph) 1 was included in the Ph 2 analysis as Cohort 4 was the established dose from Ph 1. Ph 1: radiation as 61-65 Gray (Gy) in 33-35 fractions if 2-phase treatment/62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed IV bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) through 500 mg/m\^2 on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 on Days 1-3 and 22-24 for the first 3 cohorts and cisplatin 20 mg/m\^2 on Days 1-5 and 22-26 for Cohort 4. Participants then received 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2. Ph 2: radiation, 61-65 Gy in 33-35 fractions if 2-phase treatment/62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed IV bolus from Ph 1 trial on Days 1 and 22; concurrent cisplatin from Ph 1 trial with cycles commencing on Days 1 and 22; and 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.	Pemetrexed/Cisplatin/Radiation Phase 2 n=33 participants at risk Treatment included: radiation, 61-65 Gy in 33-35 fractions if two-phase treatment and 62-66 Gy in 31-33 fractions if one-phase treatment; concurrent pemetrexed IV bolus as determined by Phase 1 trial on Days 1 and 22; concurrent cisplatin as determined by Phase 1 trial with cycles commencing on Days 1 and 22; and two additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2.
Vascular disorders Hypertension	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Blood and lymphatic system disorders Neutropenia	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Cardiac disorders Left ventricular failure	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Cardiac disorders Right ventricular failure	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Gastrointestinal disorders Oesophagitis	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	6.1% 2/33 • Number of events 2 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
General disorders Fatigue	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	6.1% 2/33 • Number of events 2 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
General disorders Oedema peripheral	20.0% 2/10 • Number of events 2 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Infections and infestations Enterocolitis infectious	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Infections and infestations Pneumonia	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Injury, poisoning and procedural complications Radiation pneumonitis	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	6.1% 2/33 • Number of events 2 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Injury, poisoning and procedural complications Vascular access complication	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Investigations Blood creatinine increased	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Investigations Haemoglobin decreased	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Investigations Neutrophil count decreased	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Investigations Platelet count decreased	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/33 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Nervous system disorders Syncope	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	6.1% 2/33 • Number of events 2 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	3.0% 1/33 • Number of events 1 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.
Vascular disorders Hypotension	0.00% 0/10 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	0.00% 0/6 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.	6.1% 2/33 • Number of events 2 • Serious Adverse Events (SAE) and other Non-Serious Adverse Events were collected during study treatment only, participants received study drug for 4 cycles of 21 days per cycle.