Trial Outcomes & Findings for Pemetrexed Plus Cisplatin Bi-Weekly, in Patients With Urothelial Cancer (Metastatic, Locally Advanced or Non-Resectable) (NCT NCT00374868)
NCT ID: NCT00374868
Last Updated: 2010-11-04
Results Overview
Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
COMPLETED
PHASE1/PHASE2
59 participants
baseline to measured progressive disease (up to 620 days)
2010-11-04
Participant Flow
A total of 59 participants entered the trial (21 in Phase 1 and 38 in Phase 2). Phase 1 determined the dose for Phase 2 to be 400 mg/m\^2. Phase 2 results are reported.
Participant milestones
| Measure |
Pemetrexed + Cisplatin
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Overall Study
STARTED
|
38
|
|
Overall Study
COMPLETED
|
2
|
|
Overall Study
NOT COMPLETED
|
36
|
Reasons for withdrawal
| Measure |
Pemetrexed + Cisplatin
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Overall Study
Adverse Event
|
12
|
|
Overall Study
Progressive Disease
|
7
|
|
Overall Study
Physician Decision
|
13
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Death
|
2
|
|
Overall Study
Other - Not Specified
|
1
|
Baseline Characteristics
Pemetrexed Plus Cisplatin Bi-Weekly, in Patients With Urothelial Cancer (Metastatic, Locally Advanced or Non-Resectable)
Baseline characteristics by cohort
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Age Continuous
|
67.1 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
38 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0 - Fully Active
|
21 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1 - Ambulatory, Restricted Strenuous Activity
|
15 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2 - Ambulatory, No Work Activities
|
2 participants
n=5 Participants
|
|
Location of Primary Tumor
Bladder
|
32 participants
n=5 Participants
|
|
Location of Primary Tumor
Ureter
|
1 participants
n=5 Participants
|
|
Location of Primary Tumor
Urethra
|
1 participants
n=5 Participants
|
|
Location of Primary Tumor
Renal Pelvis
|
4 participants
n=5 Participants
|
|
Height
|
166 centimeters
STANDARD_DEVIATION 7.5 • n=5 Participants
|
|
Weight
|
77.4 kilograms
STANDARD_DEVIATION 13.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to measured progressive disease (up to 620 days)Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Best Overall Tumor Response
Complete Response
|
2 participants
|
|
Best Overall Tumor Response
Partial Response
|
13 participants
|
|
Best Overall Tumor Response
Stable Disease
|
13 participants
|
|
Best Overall Tumor Response
Progressive Disease
|
1 participants
|
|
Best Overall Tumor Response
Not Evaluated
|
3 participants
|
|
Best Overall Tumor Response
Not Performed
|
3 participants
|
|
Best Overall Tumor Response
Missing
|
3 participants
|
SECONDARY outcome
Timeframe: baseline to response (up to 620 days)Population: 16 patients were censored.
Defined as time from study enrollment to the first Complete Response or Partial Response (using RECIST criteria). Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Time to Response
|
111.816 days
Standard Error 6.480
|
SECONDARY outcome
Timeframe: time of response to progressive disease (up to 620 days)Population: 10 patients were censored.
The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Duration of Response
|
184.100 days
Standard Error 19.595
|
SECONDARY outcome
Timeframe: time of no response or progression (up to 620 days)Population: 1 patient was censored.
Defined as time from study enrollment to the first progression of disease, complete response, partial response, or death from any cause. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Duration of Stable Disease
|
80 days
Interval 71.0 to 103.0
|
SECONDARY outcome
Timeframe: baseline to measured progressive disease (up to 620 days)Population: 19 patients were censored
Defined as the time from study enrollment to the first date of disease progression. Time to disease progression was censored at the date of death if death was due to other cause. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Time to Progressive Disease
|
260.182 days
Standard Error 22.954
|
SECONDARY outcome
Timeframe: baseline to stopping treatment (up to 620 days)Population: 1 patient was censored
Time from study enrollment to first observation of disease progression, death from any cause, or early discontinuation of treatment (including toxicity or if patient had stable disease after 4 cycles). TTF was censored at date of last follow-up visit for patients who did not discontinue early, who were still alive, and who had not progressed.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Time to Treatment Failure (TTF)
|
133.5 days
Interval 99.0 to 151.0
|
SECONDARY outcome
Timeframe: baseline to measured progressive disease (up to 620 days)Population: 11 patients were censored
Defined as the time from study enrollment until disease progression or death from any cause.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Progression-Free Survival
|
203 days
Interval 137.0 to 285.0
|
SECONDARY outcome
Timeframe: baseline to date of death from any cause (up to 620 days)Population: 20 patients were censored.
Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=38 Participants
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Overall Survival
|
264.190 days
Standard Error 15.130
|
Adverse Events
Pemetrexed + Cisplatin
Serious adverse events
| Measure |
Pemetrexed + Cisplatin
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.6%
1/38 • Number of events 3
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.6%
1/38 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.9%
3/38 • Number of events 4
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.5%
4/38 • Number of events 5
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.6%
1/38 • Number of events 1
|
|
Cardiac disorders
Cardio-respiratory arrest
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
7.9%
3/38 • Number of events 3
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
1/38 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
7.9%
3/38 • Number of events 3
|
|
General disorders
Asthenia
|
2.6%
1/38 • Number of events 1
|
|
General disorders
Pyrexia
|
7.9%
3/38 • Number of events 3
|
|
Infections and infestations
Pseudomonal sepsis
|
2.6%
1/38 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
7.9%
3/38 • Number of events 3
|
|
Investigations
Blood electrolytes abnormal
|
2.6%
1/38 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
2.6%
1/38 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.6%
1/38 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
5.3%
2/38 • Number of events 2
|
|
Renal and urinary disorders
Renal impairment
|
2.6%
1/38 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.6%
1/38 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
5.3%
2/38 • Number of events 2
|
|
Vascular disorders
Deep vein thrombosis
|
10.5%
4/38 • Number of events 4
|
Other adverse events
| Measure |
Pemetrexed + Cisplatin
Pemetrexed: phase 1 determined dose=400 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy Cisplatin: 50 mg/m2, intravenous (IV), days 1 and 15 every 28 days until disease progression, unacceptable toxicity or patient decision to discontinue or 6 cycles of therapy
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
21.1%
8/38 • Number of events 12
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.3%
2/38 • Number of events 3
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.9%
3/38 • Number of events 7
|
|
Ear and labyrinth disorders
Tinnitus
|
5.3%
2/38 • Number of events 2
|
|
Eye disorders
Conjunctivitis
|
10.5%
4/38 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.3%
2/38 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain
|
26.3%
10/38 • Number of events 10
|
|
Gastrointestinal disorders
Abdominal pain lower
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
13.2%
5/38 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
26.3%
10/38 • Number of events 18
|
|
Gastrointestinal disorders
Diarrhoea
|
47.4%
18/38 • Number of events 32
|
|
Gastrointestinal disorders
Dry mouth
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Dyspepsia
|
10.5%
4/38 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
52.6%
20/38 • Number of events 48
|
|
Gastrointestinal disorders
Stomatitis
|
5.3%
2/38 • Number of events 4
|
|
Gastrointestinal disorders
Tongue ulceration
|
5.3%
2/38 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
52.6%
20/38 • Number of events 30
|
|
General disorders
Asthenia
|
76.3%
29/38 • Number of events 82
|
|
General disorders
Chest pain
|
5.3%
2/38 • Number of events 2
|
|
General disorders
Gait disturbance
|
7.9%
3/38 • Number of events 3
|
|
General disorders
Mucosal inflammation
|
36.8%
14/38 • Number of events 33
|
|
General disorders
Oedema
|
10.5%
4/38 • Number of events 6
|
|
General disorders
Oedema peripheral
|
15.8%
6/38 • Number of events 10
|
|
General disorders
Pyrexia
|
7.9%
3/38 • Number of events 6
|
|
Infections and infestations
Influenza
|
5.3%
2/38 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
5.3%
2/38 • Number of events 2
|
|
Infections and infestations
Urinary tract infection
|
5.3%
2/38 • Number of events 2
|
|
Investigations
Alanine aminotransferase increased
|
5.3%
2/38 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
5.3%
2/38 • Number of events 2
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.3%
2/38 • Number of events 2
|
|
Investigations
Weight decreased
|
5.3%
2/38 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
50.0%
19/38 • Number of events 26
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.5%
4/38 • Number of events 4
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
5.3%
2/38 • Number of events 2
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
5.3%
2/38 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.4%
7/38 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
5.3%
2/38 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.3%
2/38 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.3%
2/38 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
7.9%
3/38 • Number of events 3
|
|
Nervous system disorders
Dysgeusia
|
18.4%
7/38 • Number of events 12
|
|
Nervous system disorders
Headache
|
7.9%
3/38 • Number of events 3
|
|
Nervous system disorders
Neuropathy
|
5.3%
2/38 • Number of events 2
|
|
Nervous system disorders
Paraesthesia
|
13.2%
5/38 • Number of events 10
|
|
Nervous system disorders
Tremor
|
5.3%
2/38 • Number of events 2
|
|
Psychiatric disorders
Depression
|
5.3%
2/38 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
7.9%
3/38 • Number of events 3
|
|
Renal and urinary disorders
Dysuria
|
7.9%
3/38 • Number of events 3
|
|
Renal and urinary disorders
Haematuria
|
5.3%
2/38 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
2/38 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.2%
5/38 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.3%
2/38 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
5.3%
2/38 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.9%
3/38 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.3%
2/38 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.5%
4/38 • Number of events 4
|
|
Vascular disorders
Deep vein thrombosis
|
5.3%
2/38 • Number of events 2
|
|
Vascular disorders
Hypertension
|
13.2%
5/38 • Number of events 5
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60