Trial Outcomes & Findings for A Study of Thymidylate Synthase Expression in Patients With Non-Small Cell Lung Cancer (NCT NCT00887549)
NCT ID: NCT00887549
Last Updated: 2012-06-19
Results Overview
PFS is time from first dose to first observation of disease progression/death (any cause). PFS is reported for participants with thymidylate synthase (TS) scores. For participants not known to have died by the data cut-off date and who do not have progressive disease, PFS will be censored at date of last objective progression-free disease assessment. For participants who receive systemic anticancer therapy after study drug discontinuation and prior to disease progression/death, PFS will be censored at date of last objective progression-free disease assessment prior to chemotherapy.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
Baseline to measured progressive disease with follow-up every 6 weeks until progression of disease (up to 18 months after the last participant commenced induction therapy)
Results posted on
2012-06-19
Participant Flow
The trial consists of induction therapy (up to 4 cycles of pemetrexed-cisplatin treatment) and maintenance therapy (pemetrexed only). Only participants who do not develop disease progression during induction therapy are eligible to receive maintenance therapy.
Participant milestones
| Measure |
Pemetrexed
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Induction Therapy
STARTED
|
70
|
|
Induction Therapy
COMPLETED
|
43
|
|
Induction Therapy
NOT COMPLETED
|
27
|
|
Maintenance Therapy
STARTED
|
43
|
|
Maintenance Therapy
COMPLETED
|
0
|
|
Maintenance Therapy
NOT COMPLETED
|
43
|
Reasons for withdrawal
| Measure |
Pemetrexed
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Induction Therapy
Adverse Event
|
8
|
|
Induction Therapy
Physician Decision
|
1
|
|
Induction Therapy
Progressive Disease
|
13
|
|
Induction Therapy
Death due to Study Disease
|
4
|
|
Induction Therapy
Death due to Study Drug Toxicity
|
1
|
|
Maintenance Therapy
Adverse Event
|
16
|
|
Maintenance Therapy
Physician Decision
|
1
|
|
Maintenance Therapy
Progressive Disease
|
25
|
|
Maintenance Therapy
Death due to adverse event
|
1
|
Baseline Characteristics
A Study of Thymidylate Synthase Expression in Patients With Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed
n=70 Participants
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Age Continuous
|
63.0 years
STANDARD_DEVIATION 9.42 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
69 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Ireland
|
4 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
66 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0- Fully active
|
24 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1- Ambulatory, Restricted Strenuous Activity
|
46 participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma, not otherwise specified (NOS)
|
34 participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma, acinar
|
1 participants
n=5 Participants
|
|
Pathological Diagnosis
Adenocarcinoma, poorly differentiated
|
20 participants
n=5 Participants
|
|
Pathological Diagnosis
Bronchioalveolar Carcinoma
|
6 participants
n=5 Participants
|
|
Pathological Diagnosis
Carcinoma, Non-Small Cell, Lung (NSCL), (NOS)
|
3 participants
n=5 Participants
|
|
Pathological Diagnosis
Carcinoma, NSC, Poorly Differentiated, Lung
|
5 participants
n=5 Participants
|
|
Pathological Diagnosis
Carcinoma, undifferentiated
|
1 participants
n=5 Participants
|
|
Past and Current Tobacco Usage
Never used tobacco products
|
6 participants
n=5 Participants
|
|
Past and Current Tobacco Usage
Ever used tobacco products
|
64 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to measured progressive disease with follow-up every 6 weeks until progression of disease (up to 18 months after the last participant commenced induction therapy)Population: Population for the efficacy assessment includes all treated participants with a valid TS expression assessment. Six participants were censored for PFS.
PFS is time from first dose to first observation of disease progression/death (any cause). PFS is reported for participants with thymidylate synthase (TS) scores. For participants not known to have died by the data cut-off date and who do not have progressive disease, PFS will be censored at date of last objective progression-free disease assessment. For participants who receive systemic anticancer therapy after study drug discontinuation and prior to disease progression/death, PFS will be censored at date of last objective progression-free disease assessment prior to chemotherapy.
Outcome measures
| Measure |
Pemetrexed
n=60 Participants
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Progression Free Survival (PFS)
|
5.5 months
Interval 3.9 to 6.9
|
SECONDARY outcome
Timeframe: Baseline to disease progression (up to 20 months)Population: All enrolled participants.
Tumor response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. Percentage of participants with tumor response was determined by the number of participants with PR or CR (confirmed or not) divided by the total number of treated participants multiplied by 100.
Outcome measures
| Measure |
Pemetrexed
n=70 Participants
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Percentage of Participants With Tumor Response (Tumor Response Rate)
|
30 percentage of participants
Interval 19.62 to 42.13
|
SECONDARY outcome
Timeframe: BaselinePopulation: All enrolled participants.
A centralized pathology review on all enrolled participants was performed to confirm the histological diagnosis performed at the site. Upon review of the local diagnosis obtained at the respective site, the central reviewer established whether or not there was an agreement between the local and central diagnosis. The percentage of participants with concordance was defined as the number of participants for which there was an agreement divided by the number of treated participants (concordance rate) multiplied by 100.
Outcome measures
| Measure |
Pemetrexed
n=70 Participants
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Percentage of Participants With Concordance Between Local and Central Histological Diagnosis
|
78.6 percentage of participants
Interval 67.1 to 87.5
|
SECONDARY outcome
Timeframe: Baseline to date of death (up to 24.5 months)Population: All enrolled participants. Nineteen participants were censored for overall survival.
The percentage of participants surviving at 18 months was defined as the number of treated participants who had not died prior to 18 months from the date of their first dose divided by the total number of treated participants multiplied by 100. For participants who are alive, overall survival was censored at the last contact.
Outcome measures
| Measure |
Pemetrexed
n=70 Participants
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Percentage of Participants Surviving at 18 Months (Overall Survival Rate)
|
37.1 percentage of participants
Interval 25.89 to 49.52
|
Adverse Events
Pemetrexed
Serious events: 41 serious events
Other events: 67 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pemetrexed
n=70 participants at risk
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.4%
1/70 • Number of events 2
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.4%
1/70 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.3%
3/70 • Number of events 3
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.4%
1/70 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
2.9%
2/70 • Number of events 2
|
|
Cardiac disorders
Atrial flutter
|
1.4%
1/70 • Number of events 1
|
|
Cardiac disorders
Pericardial effusion
|
2.9%
2/70 • Number of events 2
|
|
Cardiac disorders
Pericarditis
|
1.4%
1/70 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
1.4%
1/70 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
1.4%
1/70 • Number of events 1
|
|
Eye disorders
Ocular hyperaemia
|
1.4%
1/70 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
1.4%
1/70 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.4%
1/70 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
1.4%
1/70 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
5/70 • Number of events 5
|
|
Gastrointestinal disorders
Nausea
|
10.0%
7/70 • Number of events 7
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
7/70 • Number of events 7
|
|
General disorders
Chest discomfort
|
1.4%
1/70 • Number of events 1
|
|
General disorders
Fatigue
|
5.7%
4/70 • Number of events 4
|
|
General disorders
Non-cardiac chest pain
|
7.1%
5/70 • Number of events 5
|
|
General disorders
Oedema peripheral
|
2.9%
2/70 • Number of events 3
|
|
General disorders
Pyrexia
|
4.3%
3/70 • Number of events 3
|
|
Hepatobiliary disorders
Cholecystitis
|
1.4%
1/70 • Number of events 1
|
|
Infections and infestations
Catheter site infection
|
1.4%
1/70 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
5.7%
4/70 • Number of events 4
|
|
Infections and infestations
Lower respiratory tract infection
|
8.6%
6/70 • Number of events 6
|
|
Infections and infestations
Lung infection
|
1.4%
1/70 • Number of events 1
|
|
Infections and infestations
Neutropenic sepsis
|
2.9%
2/70 • Number of events 2
|
|
Infections and infestations
Oral candidiasis
|
2.9%
2/70 • Number of events 2
|
|
Infections and infestations
Penile infection
|
1.4%
1/70 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
4.3%
3/70 • Number of events 3
|
|
Infections and infestations
Urinary tract infection
|
1.4%
1/70 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
1.4%
1/70 • Number of events 1
|
|
Injury, poisoning and procedural complications
Vena cava injury
|
1.4%
1/70 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
1.4%
1/70 • Number of events 1
|
|
Investigations
Blood urea increased
|
1.4%
1/70 • Number of events 1
|
|
Investigations
Gamma-glutamyltransferase increased
|
1.4%
1/70 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
4.3%
3/70 • Number of events 3
|
|
Investigations
Lymphocyte count decreased
|
1.4%
1/70 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
2.9%
2/70 • Number of events 3
|
|
Investigations
Platelet count decreased
|
2.9%
2/70 • Number of events 2
|
|
Investigations
White blood cell count decreased
|
1.4%
1/70 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
4.3%
3/70 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
2.9%
2/70 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.4%
1/70 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypophagia
|
1.4%
1/70 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.4%
1/70 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.4%
1/70 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
1.4%
1/70 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.4%
1/70 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.9%
2/70 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial tumour haemorrhage
|
1.4%
1/70 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa
|
1.4%
1/70 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.4%
1/70 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
1.4%
1/70 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
1.4%
1/70 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
1.4%
1/70 • Number of events 1
|
|
Nervous system disorders
Presyncope
|
1.4%
1/70 • Number of events 1
|
|
Nervous system disorders
Syncope
|
1.4%
1/70 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
2.9%
2/70 • Number of events 2
|
|
Renal and urinary disorders
Haematuria
|
1.4%
1/70 • Number of events 1
|
|
Renal and urinary disorders
Incontinence
|
1.4%
1/70 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
2.9%
2/70 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.4%
1/70 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.7%
4/70 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.4%
1/70 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.7%
4/70 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.4%
1/70 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
1.4%
1/70 • Number of events 1
|
|
Vascular disorders
Raynaud's phenomenon
|
1.4%
1/70 • Number of events 1
|
|
Vascular disorders
Superior vena cava syndrome
|
1.4%
1/70 • Number of events 1
|
|
Vascular disorders
Vena cava thrombosis
|
1.4%
1/70 • Number of events 1
|
Other adverse events
| Measure |
Pemetrexed
n=70 participants at risk
Induction Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
21.4%
15/70 • Number of events 15
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.0%
7/70 • Number of events 10
|
|
Ear and labyrinth disorders
Tinnitus
|
7.1%
5/70 • Number of events 5
|
|
Eye disorders
Lacrimation increased
|
21.4%
15/70 • Number of events 15
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
5/70 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
32.9%
23/70 • Number of events 28
|
|
Gastrointestinal disorders
Diarrhoea
|
27.1%
19/70 • Number of events 23
|
|
Gastrointestinal disorders
Dry mouth
|
7.1%
5/70 • Number of events 5
|
|
Gastrointestinal disorders
Dyspepsia
|
14.3%
10/70 • Number of events 12
|
|
Gastrointestinal disorders
Nausea
|
47.1%
33/70 • Number of events 53
|
|
Gastrointestinal disorders
Stomatitis
|
5.7%
4/70 • Number of events 4
|
|
Gastrointestinal disorders
Vomiting
|
35.7%
25/70 • Number of events 34
|
|
General disorders
Chest pain
|
5.7%
4/70 • Number of events 4
|
|
General disorders
Fatigue
|
55.7%
39/70 • Number of events 43
|
|
General disorders
Mucosal inflammation
|
7.1%
5/70 • Number of events 5
|
|
General disorders
Oedema peripheral
|
14.3%
10/70 • Number of events 11
|
|
Infections and infestations
Cellulitis
|
7.1%
5/70 • Number of events 6
|
|
Infections and infestations
Lower respiratory tract infection
|
18.6%
13/70 • Number of events 16
|
|
Infections and infestations
Oral candidiasis
|
8.6%
6/70 • Number of events 7
|
|
Infections and infestations
Urinary tract infection
|
5.7%
4/70 • Number of events 5
|
|
Investigations
Alanine aminotransferase increased
|
11.4%
8/70 • Number of events 8
|
|
Investigations
Aspartate aminotransferase increased
|
8.6%
6/70 • Number of events 6
|
|
Investigations
Blood creatinine increased
|
15.7%
11/70 • Number of events 11
|
|
Investigations
Creatinine renal clearance decreased
|
7.1%
5/70 • Number of events 5
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.7%
4/70 • Number of events 4
|
|
Investigations
Haemoglobin decreased
|
14.3%
10/70 • Number of events 13
|
|
Investigations
Neutrophil count decreased
|
8.6%
6/70 • Number of events 9
|
|
Investigations
Weight decreased
|
8.6%
6/70 • Number of events 6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
31.4%
22/70 • Number of events 23
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.7%
4/70 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
7.1%
5/70 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
7.1%
5/70 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.1%
5/70 • Number of events 5
|
|
Nervous system disorders
Dizziness
|
5.7%
4/70 • Number of events 4
|
|
Nervous system disorders
Dysgeusia
|
17.1%
12/70 • Number of events 12
|
|
Nervous system disorders
Headache
|
18.6%
13/70 • Number of events 14
|
|
Nervous system disorders
Lethargy
|
12.9%
9/70 • Number of events 9
|
|
Nervous system disorders
Neuropathy peripheral
|
8.6%
6/70 • Number of events 7
|
|
Nervous system disorders
Tremor
|
5.7%
4/70 • Number of events 4
|
|
Psychiatric disorders
Anxiety
|
5.7%
4/70 • Number of events 4
|
|
Psychiatric disorders
Insomnia
|
7.1%
5/70 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.6%
13/70 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.4%
8/70 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.1%
5/70 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
5.7%
4/70 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.7%
4/70 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.7%
4/70 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
15.7%
11/70 • Number of events 11
|
|
Skin and subcutaneous tissue disorders
Rash
|
21.4%
15/70 • Number of events 15
|
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