Trial Outcomes & Findings for Phase II Trial of Neo-Adjuvant Pemetrexed Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma (NCT NCT00087698)
NCT ID: NCT00087698
Last Updated: 2009-05-12
Results Overview
Number of participants with results of pathological review that indicated a complete response. Pathological complete response should be evaluated at the time of surgery (Extrapleural Pneumonectomy \[EPP\]). Resected tissue or pleural fluid should be sent for pathological and histological evaluation.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
77 participants
Primary outcome timeframe
Surgery (at least 3 weeks post last dose of chemotherapy, up to a maximum interval of 8 weeks)
Results posted on
2009-05-12
Participant Flow
Participant milestones
| Measure |
Pemetrexed
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Overall Study
STARTED
|
77
|
|
Overall Study
COMPLETED
|
41
|
|
Overall Study
NOT COMPLETED
|
36
|
Reasons for withdrawal
| Measure |
Pemetrexed
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Overall Study
Lack of Efficacy, Progressive Disease
|
14
|
|
Overall Study
Death from Other Causes
|
3
|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Lack of Efficacy, Physician Perception
|
3
|
|
Overall Study
Protocol Entry Criteria Not Met
|
2
|
|
Overall Study
Clinical Relapse
|
1
|
|
Overall Study
Death from Study Disease
|
2
|
|
Overall Study
Death from Study Drug Toxicity
|
2
|
|
Overall Study
Protocol Violation
|
1
|
Baseline Characteristics
Phase II Trial of Neo-Adjuvant Pemetrexed Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma
Baseline characteristics by cohort
| Measure |
Pemetrexed
n=77 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Age Continuous
|
61.1 years
STANDARD_DEVIATION 9.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
56 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
77 participants
n=5 Participants
|
|
Disease Stage at Time of Study Entry
Stage IA
|
3 participants
n=5 Participants
|
|
Disease Stage at Time of Study Entry
Stage IB
|
3 participants
n=5 Participants
|
|
Disease Stage at Time of Study Entry
Stage II
|
33 participants
n=5 Participants
|
|
Disease Stage at Time of Study Entry
Stage III
|
35 participants
n=5 Participants
|
|
Disease Stage at Time of Study Entry
Stage IV
|
1 participants
n=5 Participants
|
|
Disease Stage at Time of Study Entry
Unknown/Not Available
|
2 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status
0 - Fully active and asymptomatic
|
28 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status
1 - Ambulatory with symptoms
|
47 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status
2 - In bed < 50% of time
|
2 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Epithelial Mesothelioma
|
62 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Mixed Cell Mesothelioma
|
2 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Sarcomatoid Mesothelioma
|
1 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Other
|
12 participants
n=5 Participants
|
|
Race/Ethnicity
Caucasian
|
71 participants
n=5 Participants
|
|
Race/Ethnicity
African
|
1 participants
n=5 Participants
|
|
Race/Ethnicity
East/Southeast Asian
|
1 participants
n=5 Participants
|
|
Race/Ethnicity
Western Asian
|
2 participants
n=5 Participants
|
|
Race/Ethnicity
Hispanic
|
2 participants
n=5 Participants
|
|
Time from Initial Pathological Diagnosis to Enrollment
|
2.19 months
STANDARD_DEVIATION 2.909 • n=5 Participants
|
PRIMARY outcome
Timeframe: Surgery (at least 3 weeks post last dose of chemotherapy, up to a maximum interval of 8 weeks)Population: All participants who had undergone surgery.
Number of participants with results of pathological review that indicated a complete response. Pathological complete response should be evaluated at the time of surgery (Extrapleural Pneumonectomy \[EPP\]). Resected tissue or pleural fluid should be sent for pathological and histological evaluation.
Outcome measures
| Measure |
Pemetrexed
n=57 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Pathological Complete Response
|
3 participants
|
SECONDARY outcome
Timeframe: 1 year and 2 yearsPopulation: All participants who had undergone surgery.
Kaplan-Meier estimates of the percentage of participants still alive at 1-year and 2-years, based upon the total number of participants who had surgery.
Outcome measures
| Measure |
Pemetrexed
n=57 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
The 1 and 2 Year Disease-Free Survival Rate (Percentage)
1-Year Disease-Free Rate
|
61.40 percentage of participants
Interval 47.53 to 72.63
|
|
The 1 and 2 Year Disease-Free Survival Rate (Percentage)
2-Year Disease-Free Rate
|
33.24 percentage of participants
Interval 21.45 to 45.47
|
SECONDARY outcome
Timeframe: baseline to measured progressive diseasePopulation: Intention to Treat analysis. All enrolled participants who were eligible for the treatment, whether or not they received the study drug.
The frequency of best overall tumor response summarized by response category. The best (unconfirmed) response recorded from the start of chemotherapy treatment until disease progression/recurrence, start of any further anti-tumor therapy, or time of surgery whichever comes first.
Outcome measures
| Measure |
Pemetrexed
n=77 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Overall Tumor Response
Complete Response
|
1 participants
|
|
Overall Tumor Response
Partial Response
|
24 participants
|
|
Overall Tumor Response
Stable Disease
|
36 participants
|
|
Overall Tumor Response
Progressive Disease
|
5 participants
|
|
Overall Tumor Response
Unknown/Unavailable
|
11 participants
|
SECONDARY outcome
Timeframe: baseline to stopping treatmentPopulation: All participants who had undergone surgery.
Time to relapse (treatment failure) is measured in months and calculated as (Date of first surgery - Date of first relapse after surgery + 1)/(365.25/12). Time to relapse will be censored at the date of the last visit or start date of further anti-tumor therapy or intervention, whichever comes first.
Outcome measures
| Measure |
Pemetrexed
n=57 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Time to Treatment Failure
|
18.30 months
Interval 1.71 to 41.89
|
SECONDARY outcome
Timeframe: baseline to measured progressive diseasePopulation: All participants who had undergone surgery.
Number of months between the first dose date and the date of first disease progression or death as a result of any cause, whichever comes first.
Outcome measures
| Measure |
Pemetrexed
n=57 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Time to Progressive Disease
|
14.98 months
Interval 2.56 to 46.0
|
SECONDARY outcome
Timeframe: baseline to date of death from any causePopulation: All participants who had undergone surgery.
Number of months between the first dose date and the date of death as a result of any cause. Overall survival time calculated as (Date of death - First dose date + 1)/(365.25/12).
Outcome measures
| Measure |
Pemetrexed
n=57 Participants
pemetrexed: 500 mg/m2, intravenous, every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous, every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 gray (Gy)
|
|---|---|
|
Overall Survival Time
|
21.85 months
Interval 3.25 to 46.0
|
Adverse Events
Pemetrexed
Serious events: 15 serious events
Other events: 77 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed
pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 Gy
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.6%
2/77 • Number of events 2
|
|
Cardiac disorders
Atrial fibrillation
|
1.3%
1/77 • Number of events 1
|
|
Cardiac disorders
Sinus bradycardia
|
1.3%
1/77 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
2/77 • Number of events 2
|
|
General disorders
Chest pain
|
1.3%
1/77 • Number of events 3
|
|
General disorders
Death
|
1.3%
1/77 • Number of events 1
|
|
Infections and infestations
Infection
|
1.3%
1/77 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
5.2%
4/77 • Number of events 5
|
|
Investigations
Blood creatinine increased
|
2.6%
2/77 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
1.3%
1/77 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/77 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
1.3%
1/77 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
1.3%
1/77 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/77 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
2.6%
2/77 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.6%
2/77 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.3%
1/77 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
1.3%
1/77 • Number of events 1
|
Other adverse events
| Measure |
Pemetrexed
pemetrexed: 500 mg/m2, intravenous (IV), every 21 days x 4 cycles cisplatin: 75 mg/m2, intravenous (IV), every 21 days x 4 cycles chemotherapy, surgery then chest radiation x 54 Gy
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
22.1%
17/77 • Number of events 22
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.5%
5/77 • Number of events 8
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.4%
8/77 • Number of events 10
|
|
Cardiac disorders
Tachycardia
|
9.1%
7/77 • Number of events 7
|
|
Ear and labyrinth disorders
Tinnitus
|
15.6%
12/77 • Number of events 13
|
|
Eye disorders
Lacrimation increased
|
6.5%
5/77 • Number of events 5
|
|
Eye disorders
Vision blurred
|
6.5%
5/77 • Number of events 6
|
|
Gastrointestinal disorders
Abdominal distention
|
5.2%
4/77 • Number of events 6
|
|
Gastrointestinal disorders
Abdominal pain
|
6.5%
5/77 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
58.4%
45/77 • Number of events 62
|
|
Gastrointestinal disorders
Diarrhoea
|
26.0%
20/77 • Number of events 21
|
|
Gastrointestinal disorders
Dyspepsia
|
10.4%
8/77 • Number of events 9
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.2%
4/77 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
74.0%
57/77 • Number of events 87
|
|
Gastrointestinal disorders
Stomatitis
|
19.5%
15/77 • Number of events 15
|
|
Gastrointestinal disorders
Vomiting
|
44.2%
34/77 • Number of events 47
|
|
General disorders
Chest discomfort
|
9.1%
7/77 • Number of events 8
|
|
General disorders
Chest pain
|
11.7%
9/77 • Number of events 10
|
|
General disorders
Chills
|
6.5%
5/77 • Number of events 5
|
|
General disorders
Fatigue
|
66.2%
51/77 • Number of events 79
|
|
General disorders
Oedema peripheral
|
11.7%
9/77 • Number of events 12
|
|
General disorders
Pain
|
6.5%
5/77 • Number of events 5
|
|
General disorders
Pyrexia
|
13.0%
10/77 • Number of events 12
|
|
Immune system disorders
Drug hypersensitivity
|
7.8%
6/77 • Number of events 8
|
|
Investigations
Blood creatinine increased
|
7.8%
6/77 • Number of events 8
|
|
Investigations
Breath sounds abnormal
|
10.4%
8/77 • Number of events 8
|
|
Investigations
Haemoglobin decreased
|
5.2%
4/77 • Number of events 4
|
|
Investigations
Weight decreased
|
5.2%
4/77 • Number of events 5
|
|
Investigations
White blood cell count decreased
|
5.2%
4/77 • Number of events 4
|
|
Metabolism and nutrition disorders
Anorexia
|
28.6%
22/77 • Number of events 25
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.8%
6/77 • Number of events 6
|
|
Metabolism and nutrition disorders
Dehydration
|
5.2%
4/77 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.2%
4/77 • Number of events 4
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.8%
6/77 • Number of events 7
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
7.8%
6/77 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.0%
10/77 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
5/77 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.2%
4/77 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.5%
5/77 • Number of events 5
|
|
Nervous system disorders
Dizziness
|
9.1%
7/77 • Number of events 7
|
|
Nervous system disorders
Dysgeusia
|
20.8%
16/77 • Number of events 16
|
|
Nervous system disorders
Headache
|
13.0%
10/77 • Number of events 13
|
|
Nervous system disorders
Neuropathy
|
6.5%
5/77 • Number of events 6
|
|
Nervous system disorders
Parosmia
|
5.2%
4/77 • Number of events 4
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
6.5%
5/77 • Number of events 5
|
|
Psychiatric disorders
Anxiety
|
10.4%
8/77 • Number of events 8
|
|
Psychiatric disorders
Insomnia
|
13.0%
10/77 • Number of events 10
|
|
Renal and urinary disorders
Pollakiuria
|
5.2%
4/77 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.4%
18/77 • Number of events 19
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.6%
12/77 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.5%
5/77 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
7.8%
6/77 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.4%
8/77 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.8%
6/77 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Rash
|
23.4%
18/77 • Number of events 24
|
|
Vascular disorders
Flushing
|
6.5%
5/77 • Number of events 5
|
|
Vascular disorders
Hypertension
|
7.8%
6/77 • Number of events 6
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 1-800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60