A Study of Pemetrexed and Cisplatin, in Non Small Cell Lung Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01000480
• Collaborator: (none)
• Enrollment: 90
• Locations: 21
• Arm: 1
• Duration (Months): 45
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial investigates pemetrexed and cisplatin followed by pemetrexed and cisplatin in combination with radiotherapy in participants with locally advanced, non-small cell lung cancer (NSCLC). The purpose of the study is to assess the antitumor activity as measured by progression free survival 1 year after start of treatment with study drug.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Pemetrexed; Drug: Cisplatin; Radiation: Thoracic Radiotherapy	Phase 2

Detailed Description

The participants will receive 2 cycles of pemetrexed and cisplatin. If the participants achieve complete response, partial response or stable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, have ≤35% of the total calculated lung volume receive more than 20 Gy (V20) according to the 3-dimensional (3-D) radiotherapy planning Dose Volume Histograms, have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, have no residual neurological toxicity > Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE), they will receive 2 additional cycles of pemetrexed and cisplatin, combined with radiotherapy. The combination of radiotherapy will begin 22 to 36 days after completion of the second infusion of induction therapy with pemetrexed-cisplatin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Pemetrexed and Cisplatin as Induction, Followed by Pemetrexed and Cisplatin With Concurrent Thoracic Radiotherapy, in Patients With Unresectable, Locally Advanced, Stage III, Nonsquamous Non-Small Cell Lung Cancer
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Pemetrexed Pemetrexed and cisplatin are given as induction therapy followed after by pemetrexed and cisplatin with concurrent radiotherapy.

Drug: Pemetrexed; 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of a 21 day cycle for 2 cycles: with possibility of 2 additional cycles.; Other Names: Alimta LY231514 ; Drug: Cisplatin; 75 mg/m² intravenous infusion on Day 1 of a 21 day cycle for 2 cycles; with the possibility of 2 additional cycles.; Radiation: Thoracic Radiotherapy; Administered at 2 gray (Gy)/fraction after completion of the pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and will continue daily (5 days per week) until the total delivered dose reaches a therapeutic goal of 66 Gy, over approximately 7 weeks.

Outcome Measures

Primary Outcome Measures

1. 1 Year Progression Free Survival [Date of first dose to date of objectively determined PD or death [every cycle up to 4 cycles and then every 3 months up to 1 year (1 cycle=21 days)]]

   Progression free survival (PFS) was defined as the time from study enrollment to the first observation of progressive disease (PD) or death from any cause. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study drug) prior to objectively determined PD or death, PFS was censored at the date of the last objective progression-free disease assessment prior to start of postdiscontinuation chemotherapy. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant.

Secondary Outcome Measures

1. Overall Survival [Date of first dose to date of death (up to 35.4 months)]

   Overall survival (OS) was the duration from enrollment to death due to any cause. Participants who were alive were censored at the last contact.

2. Number of Participants With an Objective Tumor Response [Date of first dose through end of follow-up [up to 30 weeks (1 cycle=21 days)]]

   Participants with confirmed complete response (CR), confirmed partial response (PR), stable disease (SD), or progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria, as well as participants with a not evaluable/tumor response unknown. CR: disappearance of all tumor lesions. PR: either a) at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as a reference baseline sum LDs, or b) complete disappearance of target lesions, with persistence (not worsening) of 1 or more nontarget lesions. In either case, no new lesions appeared. SD: small changes that did not meet above criteria. PD: at least a 20% increase in sum of LD of target lesions taking as reference smallest sum LD recorded since treatment started or appearance of 1 or more new lesions. Participants who discontinued study treatment (for reasons other than progression) before entering concurrent phase were considered to have non-evaluable response.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic or cytologic diagnosis of unresectable nonsquamous Stage IIIA or Stage IIIB (without malignant pleural/pericardial effusions) NSCLC.

• Have an ECOG performance status of 0 or 1.

• Previous radiation therapy should have been limited and must not have included thoracic radiation, whole pelvis radiation, or radiation to >25% of the participant's bone marrow, participants must have recovered from the toxic effects of radiation treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry.

• Have at least 1 unidimensionally measurable lesion meeting RECIST guidelines, version 1.0.

• Estimated life expectancy of at least 12 weeks.

• Participant compliance and geographic proximity that allow adequate follow-up.

• Adequate bone marrow reserve, hepatic-, renal- and pulmonary function.

• Participants must sign an Informed Consent Document.

• Participants must have a total lung V20 less than or equal to 35%.

• For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen, during and for 6 months after the treatment period; must have a negative serum pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.

• Have not received prior systemic anticancer therapy for NSCLC.

Exclusion Criteria:

• Have received treatment within the last 30 days of enrollment with a drug that has not received regulatory approval for any indication at the time of study entry.

• Have previously completed or withdrawn from this study or any other study investigating pemetrexed.

• Have a serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.

• Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV.

• Have had a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or non-melanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Participants with a history of low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.

• Are receiving concurrent administration of any other antitumor therapy.

• Have had weight loss of more than 10% over the previous 3 months before study entry.

• Are unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose less than or equal to 1.3 grams per day, for at least 2 days before (5 days for long-acting agents), the day of, and for at least 2 days after administration of pemetrexed.

• Are unable or unwilling to take folic acid or vitamin B12 supplementation.

• Are unable or unwilling to take corticosteroids.

• Have received a recent yellow fever vaccination (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination.

• Have known hypersensitivity to pemetrexed, cisplatin, or any of the excipients in these medicinal products.

• Have evidence of clinical hearing loss.

• Have clinically significant third-space fluid collections, that cannot be controlled by drainage or other procedures prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Le Mans		France	72000
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lyon		France	69373
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montpellier		France	34070
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Paris		France	75015
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toulouse		France	31300
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	14165
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hemer		Germany	58675
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Köln		Germany	51109
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lübeck		Germany	23538
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nürnberg		Germany	90419
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Avellino		Italy	50019
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Firenze		Italy	50139
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Milano		Italy	20132
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monza		Italy	20900
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orbassano		Italy	10043
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Perugia		Italy	06156
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08036
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid		Spain	28034
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sabadell		Spain	08208
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sevilla		Spain	41013
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Valencia		Spain	46010

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM-5 PM Eastern time (UTC/GMT- 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01000480
• Other Study ID Numbers: 13099; H3E-EW-S128
• First Posted: Oct 23, 2009
• Last Update Posted: Apr 2, 2014
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pemetrexed

Study Results

Participant Flow

Pre-assignment Detail	Study treatment had 2 phases and follow-up. Induction phase: 2 cycles of pemetrexed-cisplatin. Then, if eligible, the concurrent phase: 2 more cycles of pemetrexed-cisplatin and thoracic radiotherapy. Follow-up period: Started when treatment discontinued or completed, and lasted up to 2 years after first dose of pemetrexed.

Arm/Group Title	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Arm/Group Description	Induction phase (2 cycles). Pemetrexed: 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of 21-day cycle. Cisplatin: 75 mg/m² intravenous infusion on Day 1 of 21-day cycle. Participants eligible for concurrent phase (2 more cycles of pemetrexed-cisplatin treatment and radiotherapy) if they had complete response, partial response, or stable disease (Response Evaluation Criteria in Solid Tumors guidelines), total lung volume receiving more than 20 gray (Gy) ≤35% (dose volume histogram), 0 or 1 Eastern Cooperative Oncology Group performance status, no residual neurological toxicity >Grade 2 (Common Terminology Criteria for Adverse Events). Thoracic Radiotherapy: 2 Gy/fraction after completion of pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and continued daily (5 days per week) until total delivered dose was 66 Gy, over approximately 7 weeks. Folic acid, Vitamin B12 supplements, and prophylactic dexamethasone administered per approved pemetrexed label.
Period Title: Induction Phase
STARTED	90
Received at Least 1 Dose of Either Drug	90
Death (Any Cause) or Disease Progression	8
COMPLETED	83
NOT COMPLETED	7
Period Title: Induction Phase
STARTED	75
Death (Any Cause) or Disease Progression	1
COMPLETED	65
NOT COMPLETED	10
Period Title: Induction Phase
STARTED	88
COMPLETED	88
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Arm/Group Description	Induction phase (2 cycles). Pemetrexed: 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of 21-day cycle. Cisplatin: 75 mg/m² intravenous infusion on Day 1 of 21-day cycle. Participants eligible for concurrent phase (2 more cycles of pemetrexed-cisplatin treatment and radiotherapy) if they had complete response, partial response, or stable disease (Response Evaluation Criteria in Solid Tumors guidelines), total lung volume receiving more than 20 gray (Gy) ≤35% (dose volume histogram), 0 or 1 Eastern Cooperative Oncology Group performance status, no residual neurological toxicity >Grade 2 (Common Terminology Criteria for Adverse Events). Thoracic Radiotherapy: 2 Gy/fraction after completion of pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and continued daily (5 days per week) until total delivered dose was 66 Gy, over approximately 7 weeks. Folic acid, Vitamin B12 supplements, and prophylactic dexamethasone administered per approved pemetrexed label.
Overall Participants	90
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (8.15)
Sex: Female, Male (Count of Participants)
Female	39 43.3%
Male	51 56.7%
Race/Ethnicity, Customized (participants) [Number]
White	90 100%
Region of Enrollment (participants) [Number]
France	9 10%
Spain	17 18.9%
Germany	42 46.7%
Italy	22 24.4%
Stage of Disease (participants) [Number]
Stage IIIA	32 35.6%
Stage IIIB	56 62.2%
Stage IV	2 2.2%
Eastern Cooperative Oncology Group (ECOG) performance status (PS) (participants) [Number]
ECOG PS=0	59 65.6%
ECOG PS=1	31 34.4%
ECOG PS=2	0 0%
Initial pathological diagnosis (participants) [Number]
Adenocarcinoma (lung)	81 90%
Carcinoma (large cell, lung)	7 7.8%
Carcinoma (non-small cell, lung, NOS)	1 1.1%
Carcinoma (non-small cell, poorly differentiated)	1 1.1%
Current Tobacco Use (participants) [Number]
Never used tobacco	7 7.8%
Former user of tobacco	55 61.1%
Current use of tobacco	28 31.1%

Outcome Measures

1. Primary Outcome

Title	1 Year Progression Free Survival
Description	Progression free survival (PFS) was defined as the time from study enrollment to the first observation of progressive disease (PD) or death from any cause. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study drug) prior to objectively determined PD or death, PFS was censored at the date of the last objective progression-free disease assessment prior to start of postdiscontinuation chemotherapy. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant.
Time Frame	Date of first dose to date of objectively determined PD or death [every cycle up to 4 cycles and then every 3 months up to 1 year (1 cycle=21 days)]

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received at least 1 dose of either study drug (pemetrexed or cisplatin). The number of participants censored was 35.

Arm/Group Title	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Arm/Group Description	Induction phase (2 cycles). Pemetrexed: 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of 21-day cycle. Cisplatin: 75 mg/m² intravenous infusion on Day 1 of 21-day cycle. Participants eligible for concurrent phase (2 more cycles of pemetrexed-cisplatin treatment and radiotherapy) if they had complete response, partial response, or stable disease (Response Evaluation Criteria in Solid Tumors guidelines), total lung volume receiving more than 20 gray (Gy) ≤35% (dose volume histogram), 0 or 1 Eastern Cooperative Oncology Group performance status, no residual neurological toxicity >Grade 2 (Common Terminology Criteria for Adverse Events). Thoracic Radiotherapy: 2 Gy/fraction after completion of pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and continued daily (5 days per week) until total delivered dose was 66 Gy, over approximately 7 weeks. Folic acid, Vitamin B12 supplements, and prophylactic dexamethasone administered per approved pemetrexed label.
Measure Participants	90
Number (95% Confidence Interval) [percentage of participants]	53.7 59.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
	Comments	Null hypothesis (H0): 1-year PFS ≤45% and the alternative hypothesis (H1): 1-year PFS ≥60%, at a 2-sided alpha level of 5%, assuming that PFS time followed an exponential distribution.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0645
	Comments	P-value for H0 which compared the investigational regimen to historical data.
	Method	maximum likelihood estimate
	Comments

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was the duration from enrollment to death due to any cause. Participants who were alive were censored at the last contact.
Time Frame	Date of first dose to date of death (up to 35.4 months)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: participants who received at least 1 dose of study drug (pemetrexed or cisplatin). The number of participants censored was 45.

Arm/Group Title	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Arm/Group Description	Induction phase (2 cycles). Pemetrexed: 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of 21-day cycle. Cisplatin: 75 mg/m² intravenous infusion on Day 1 of 21-day cycle. Participants eligible for concurrent phase (2 more cycles of pemetrexed-cisplatin treatment and radiotherapy) if they had complete response, partial response, or stable disease (Response Evaluation Criteria in Solid Tumors guidelines), total lung volume receiving more than 20 gray (Gy) ≤35% (dose volume histogram), 0 or 1 Eastern Cooperative Oncology Group performance status, no residual neurological toxicity >Grade 2 (Common Terminology Criteria for Adverse Events). Thoracic Radiotherapy: 2 Gy/fraction after completion of pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and continued daily (5 days per week) until total delivered dose was 66 Gy, over approximately 7 weeks. Folic acid, Vitamin B12 supplements, and prophylactic dexamethasone administered per approved pemetrexed label.
Measure Participants	90
Median (95% Confidence Interval) [months]	26.2

3. Secondary Outcome

Title	Number of Participants With an Objective Tumor Response
Description	Participants with confirmed complete response (CR), confirmed partial response (PR), stable disease (SD), or progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria, as well as participants with a not evaluable/tumor response unknown. CR: disappearance of all tumor lesions. PR: either a) at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as a reference baseline sum LDs, or b) complete disappearance of target lesions, with persistence (not worsening) of 1 or more nontarget lesions. In either case, no new lesions appeared. SD: small changes that did not meet above criteria. PD: at least a 20% increase in sum of LD of target lesions taking as reference smallest sum LD recorded since treatment started or appearance of 1 or more new lesions. Participants who discontinued study treatment (for reasons other than progression) before entering concurrent phase were considered to have non-evaluable response.
Time Frame	Date of first dose through end of follow-up [up to 30 weeks (1 cycle=21 days)]

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: Participants who received at least 1 dose of study drug (pemetrexed or cisplatin).

Arm/Group Title	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Arm/Group Description	Induction phase (2 cycles). Pemetrexed: 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of 21-day cycle. Cisplatin: 75 mg/m² intravenous infusion on Day 1 of 21-day cycle. Participants eligible for concurrent phase (2 more cycles of pemetrexed-cisplatin treatment and radiotherapy) if they had complete response, partial response, or stable disease (Response Evaluation Criteria in Solid Tumors guidelines), total lung volume receiving more than 20 gray (Gy) ≤35% (dose volume histogram), 0 or 1 Eastern Cooperative Oncology Group performance status, no residual neurological toxicity >Grade 2 (Common Terminology Criteria for Adverse Events). Thoracic Radiotherapy: 2 Gy/fraction after completion of pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and continued daily (5 days per week) until total delivered dose was 66 Gy, over approximately 7 weeks. Folic acid, Vitamin B12 supplements, and prophylactic dexamethasone administered per approved pemetrexed label.
Measure Participants	90
Complete Response	9 10%
Partial Response	45 50%
Stable Disease	16 17.8%
Disease Progression	12 13.3%
Not evaluable/Response unknown	8 8.9%

Adverse Events

Arm/Group Title	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Arm/Group Description	Induction phase (2 cycles). Pemetrexed: 500 milligrams per square meter (mg/m²) intravenous infusion on Day 1 of 21-day cycle. Cisplatin: 75 mg/m² intravenous infusion on Day 1 of 21-day cycle. Participants eligible for concurrent phase (2 more cycles of pemetrexed-cisplatin treatment and radiotherapy) if they had complete response, partial response, or stable disease (Response Evaluation Criteria in Solid Tumors guidelines), total lung volume receiving more than 20 gray (Gy) ≤35% (dose volume histogram), 0 or 1 Eastern Cooperative Oncology Group performance status, no residual neurological toxicity >Grade 2 (Common Terminology Criteria for Adverse Events). Thoracic Radiotherapy: 2 Gy/fraction after completion of pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and continued daily (5 days per week) until total delivered dose was 66 Gy, over approximately 7 weeks. Folic acid, Vitamin B12 supplements, and prophylactic dexamethasone administered per approved pemetrexed label.
All Cause Mortality
	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
	Affected / at Risk (%)	# Events
Total	23/90 (25.6%)
Blood and lymphatic system disorders
Leukopenia	1/90 (1.1%)	1
Ear and labyrinth disorders
Hypoacusis	1/90 (1.1%)	1
Gastrointestinal disorders
Constipation	1/90 (1.1%)	1
Enteritis	1/90 (1.1%)	1
Gastritis erosive	1/90 (1.1%)	1
Nausea	1/90 (1.1%)	1
General disorders
Asthenia	1/90 (1.1%)	1
General physical health deterioration	2/90 (2.2%)	2
Pyrexia	1/90 (1.1%)	1
Infections and infestations
Device related infection	1/90 (1.1%)	1
Pneumonia	1/90 (1.1%)	1
Septic shock	1/90 (1.1%)	1
Injury, poisoning and procedural complications
Radiation oesophagitis	8/90 (8.9%)	9
Metabolism and nutrition disorders
Dehydration	2/90 (2.2%)	2
Hyponatraemia	1/90 (1.1%)	1
Nervous system disorders
Cerebrovascular accident	1/90 (1.1%)	1
Paraesthesia	1/90 (1.1%)	1
Syncope	1/90 (1.1%)	1
Renal and urinary disorders
Renal impairment	1/90 (1.1%)	1
Urinary retention	1/90 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	4/90 (4.4%)	4
Other (Not Including Serious) Adverse Events
	Pemetrexed, Cisplatin, and Thoracic Radiotherapy
	Affected / at Risk (%)	# Events
Total	85/90 (94.4%)
Blood and lymphatic system disorders
Anaemia	7/90 (7.8%)	8
Leukopenia	12/90 (13.3%)	13
Lymphopenia	6/90 (6.7%)	11
Neutropenia	17/90 (18.9%)	22
Thrombocytopenia	5/90 (5.6%)	5
Ear and labyrinth disorders
Vertigo	6/90 (6.7%)	6
Eye disorders
Conjunctivitis	6/90 (6.7%)	6
Gastrointestinal disorders
Constipation	22/90 (24.4%)	26
Diarrhoea	8/90 (8.9%)	8
Dyspepsia	7/90 (7.8%)	7
Dysphagia	27/90 (30%)	27
Nausea	43/90 (47.8%)	67
Oesophagitis	23/90 (25.6%)	25
Stomatitis	10/90 (11.1%)	12
Vomiting	11/90 (12.2%)	15
General disorders
Asthenia	18/90 (20%)	23
Chest pain	5/90 (5.6%)	8
Fatigue	14/90 (15.6%)	16
Pyrexia	8/90 (8.9%)	10
Injury, poisoning and procedural complications
Radiation oesophagitis	10/90 (11.1%)	10
Radiation skin injury	10/90 (11.1%)	10
Investigations
Haemoglobin decreased	7/90 (7.8%)	7
Neutrophil count decreased	5/90 (5.6%)	6
White blood cell count decreased	5/90 (5.6%)	7
Metabolism and nutrition disorders
Decreased appetite	8/90 (8.9%)	11
Musculoskeletal and connective tissue disorders
Back pain	6/90 (6.7%)	6
Nervous system disorders
Dizziness	7/90 (7.8%)	7
Dysgeusia	7/90 (7.8%)	9
Respiratory, thoracic and mediastinal disorders
Cough	14/90 (15.6%)	14
Dyspnoea	13/90 (14.4%)	14
Skin and subcutaneous tissue disorders
Rash	6/90 (6.7%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.