Trial Outcomes & Findings for A Study of Pemetrexed and Cisplatin, in Non Small Cell Lung Cancer (NCT NCT01000480)
NCT ID: NCT01000480
Last Updated: 2014-04-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
90 participants
Primary outcome timeframe
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)]
Results posted on
2014-04-02
Participant Flow
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.
Participant milestones
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
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.
|
|---|---|
|
Induction Phase
STARTED
|
90
|
|
Induction Phase
Received at Least 1 Dose of Either Drug
|
90
|
|
Induction Phase
Death (Any Cause) or Disease Progression
|
8
|
|
Induction Phase
COMPLETED
|
83
|
|
Induction Phase
NOT COMPLETED
|
7
|
|
Concurrent Therapy Phase
STARTED
|
75
|
|
Concurrent Therapy Phase
Death (Any Cause) or Disease Progression
|
1
|
|
Concurrent Therapy Phase
COMPLETED
|
65
|
|
Concurrent Therapy Phase
NOT COMPLETED
|
10
|
|
Follow-Up Period
STARTED
|
88
|
|
Follow-Up Period
COMPLETED
|
88
|
|
Follow-Up Period
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
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.
|
|---|---|
|
Induction Phase
Adverse Event
|
2
|
|
Induction Phase
Lost to Follow-up
|
1
|
|
Induction Phase
Physician Decision
|
1
|
|
Induction Phase
Entry Criteria Not Met
|
3
|
|
Concurrent Therapy Phase
Adverse Event
|
4
|
|
Concurrent Therapy Phase
Protocol Violation
|
2
|
|
Concurrent Therapy Phase
Withdrawal by Subject
|
3
|
|
Concurrent Therapy Phase
Physician Decision
|
1
|
Baseline Characteristics
A Study of Pemetrexed and Cisplatin, in Non Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
n=90 Participants
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.
|
|---|---|
|
Age, Continuous
|
61.7 years
STANDARD_DEVIATION 8.15 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
90 participants
n=5 Participants
|
|
Region of Enrollment
France
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
17 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
42 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
22 participants
n=5 Participants
|
|
Stage of Disease
Stage IIIA
|
32 participants
n=5 Participants
|
|
Stage of Disease
Stage IIIB
|
56 participants
n=5 Participants
|
|
Stage of Disease
Stage IV
|
2 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status (PS)
ECOG PS=0
|
59 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status (PS)
ECOG PS=1
|
31 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status (PS)
ECOG PS=2
|
0 participants
n=5 Participants
|
|
Initial pathological diagnosis
Adenocarcinoma (lung)
|
81 participants
n=5 Participants
|
|
Initial pathological diagnosis
Carcinoma (large cell, lung)
|
7 participants
n=5 Participants
|
|
Initial pathological diagnosis
Carcinoma (non-small cell, lung, NOS)
|
1 participants
n=5 Participants
|
|
Initial pathological diagnosis
Carcinoma (non-small cell, poorly differentiated)
|
1 participants
n=5 Participants
|
|
Current Tobacco Use
Never used tobacco
|
7 participants
n=5 Participants
|
|
Current Tobacco Use
Former user of tobacco
|
55 participants
n=5 Participants
|
|
Current Tobacco Use
Current use of tobacco
|
28 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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)]Population: 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.
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.
Outcome measures
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
n=90 Participants
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.
|
|---|---|
|
1 Year Progression Free Survival
|
53.7 percentage of participants
Interval 44.8 to 62.5
|
SECONDARY outcome
Timeframe: Date of first dose to date of death (up to 35.4 months)Population: Intent-to-treat population: participants who received at least 1 dose of study drug (pemetrexed or cisplatin). The number of participants censored was 45.
Overall survival (OS) was the duration from enrollment to death due to any cause. Participants who were alive were censored at the last contact.
Outcome measures
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
n=90 Participants
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 Survival
|
26.2 months
Interval 16.7 to
The upper 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: Date of first dose through end of follow-up [up to 30 weeks (1 cycle=21 days)]Population: Intent-to-treat population: Participants who received at least 1 dose of study drug (pemetrexed or cisplatin).
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.
Outcome measures
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
n=90 Participants
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.
|
|---|---|
|
Number of Participants With an Objective Tumor Response
Complete Response
|
9 participants
|
|
Number of Participants With an Objective Tumor Response
Partial Response
|
45 participants
|
|
Number of Participants With an Objective Tumor Response
Stable Disease
|
16 participants
|
|
Number of Participants With an Objective Tumor Response
Disease Progression
|
12 participants
|
|
Number of Participants With an Objective Tumor Response
Not evaluable/Response unknown
|
8 participants
|
Adverse Events
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
Serious events: 23 serious events
Other events: 85 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
n=90 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
1.1%
1/90 • Number of events 1
|
|
Ear and labyrinth disorders
Hypoacusis
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Enteritis
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis erosive
|
1.1%
1/90 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
1.1%
1/90 • Number of events 1
|
|
General disorders
Asthenia
|
1.1%
1/90 • Number of events 1
|
|
General disorders
General physical health deterioration
|
2.2%
2/90 • Number of events 2
|
|
General disorders
Pyrexia
|
1.1%
1/90 • Number of events 1
|
|
Infections and infestations
Device related infection
|
1.1%
1/90 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
1.1%
1/90 • Number of events 1
|
|
Infections and infestations
Septic shock
|
1.1%
1/90 • Number of events 1
|
|
Injury, poisoning and procedural complications
Radiation oesophagitis
|
8.9%
8/90 • Number of events 9
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
2/90 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.1%
1/90 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
1.1%
1/90 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
1.1%
1/90 • Number of events 1
|
|
Nervous system disorders
Syncope
|
1.1%
1/90 • Number of events 1
|
|
Renal and urinary disorders
Renal impairment
|
1.1%
1/90 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
1.1%
1/90 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.4%
4/90 • Number of events 4
|
Other adverse events
| Measure |
Pemetrexed, Cisplatin, and Thoracic Radiotherapy
n=90 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.8%
7/90 • Number of events 8
|
|
Blood and lymphatic system disorders
Leukopenia
|
13.3%
12/90 • Number of events 13
|
|
Blood and lymphatic system disorders
Lymphopenia
|
6.7%
6/90 • Number of events 11
|
|
Blood and lymphatic system disorders
Neutropenia
|
18.9%
17/90 • Number of events 22
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
5/90 • Number of events 5
|
|
Ear and labyrinth disorders
Vertigo
|
6.7%
6/90 • Number of events 6
|
|
Eye disorders
Conjunctivitis
|
6.7%
6/90 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
24.4%
22/90 • Number of events 26
|
|
Gastrointestinal disorders
Diarrhoea
|
8.9%
8/90 • Number of events 8
|
|
Gastrointestinal disorders
Dyspepsia
|
7.8%
7/90 • Number of events 7
|
|
Gastrointestinal disorders
Dysphagia
|
30.0%
27/90 • Number of events 27
|
|
Gastrointestinal disorders
Nausea
|
47.8%
43/90 • Number of events 67
|
|
Gastrointestinal disorders
Oesophagitis
|
25.6%
23/90 • Number of events 25
|
|
Gastrointestinal disorders
Stomatitis
|
11.1%
10/90 • Number of events 12
|
|
Gastrointestinal disorders
Vomiting
|
12.2%
11/90 • Number of events 15
|
|
General disorders
Asthenia
|
20.0%
18/90 • Number of events 23
|
|
General disorders
Chest pain
|
5.6%
5/90 • Number of events 8
|
|
General disorders
Fatigue
|
15.6%
14/90 • Number of events 16
|
|
General disorders
Pyrexia
|
8.9%
8/90 • Number of events 10
|
|
Injury, poisoning and procedural complications
Radiation oesophagitis
|
11.1%
10/90 • Number of events 10
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
11.1%
10/90 • Number of events 10
|
|
Investigations
Haemoglobin decreased
|
7.8%
7/90 • Number of events 7
|
|
Investigations
Neutrophil count decreased
|
5.6%
5/90 • Number of events 6
|
|
Investigations
White blood cell count decreased
|
5.6%
5/90 • Number of events 7
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.9%
8/90 • Number of events 11
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
6/90 • Number of events 6
|
|
Nervous system disorders
Dizziness
|
7.8%
7/90 • Number of events 7
|
|
Nervous system disorders
Dysgeusia
|
7.8%
7/90 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.6%
14/90 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.4%
13/90 • Number of events 14
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.7%
6/90 • Number of events 6
|
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