Trial Outcomes & Findings for Gemcitabine Monotherapy for Metastatic Breast Cancer After Anthracycline and Taxane Regimen (NCT NCT00191269)
NCT ID: NCT00191269
Last Updated: 2010-03-17
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
68 participants
Primary outcome timeframe
baseline to measured progressive disease
Results posted on
2010-03-17
Participant Flow
At Step 1, 6 participants each were assigned at Dose Level 1 (gemcitabine:1000 mg/ m2) and Dose Level 2 (gemcitabine:1250 mg/ m2) to determine the recommended dose for Step 2. At Step 2, an additional 56 participants received the recommended dose (Dose Level 2).
Participant milestones
| Measure |
Dose Level 1
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
62
|
|
Overall Study
COMPLETED
|
0
|
4
|
|
Overall Study
NOT COMPLETED
|
6
|
58
|
Reasons for withdrawal
| Measure |
Dose Level 1
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
2
|
|
Overall Study
Adverse Event
|
1
|
4
|
|
Overall Study
Progression of Disease
|
4
|
42
|
|
Overall Study
Lack of Efficacy
|
1
|
5
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Pathologic Aggrevation
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
3
|
Baseline Characteristics
Gemcitabine Monotherapy for Metastatic Breast Cancer After Anthracycline and Taxane Regimen
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=6 Participants
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
n=62 Participants
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
53.3 years
STANDARD_DEVIATION 7.45 • n=5 Participants
|
52.4 years
STANDARD_DEVIATION 11.25 • n=7 Participants
|
52.5 years
STANDARD_DEVIATION 10.93 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
68.0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0.0 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
6 participants
n=5 Participants
|
62 participants
n=7 Participants
|
68.0 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0 - Fully Active
|
4 participants
n=5 Participants
|
45 participants
n=7 Participants
|
49.0 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1 - Ambulatory, Restricted Strenuous Activity
|
2 participants
n=5 Participants
|
17 participants
n=7 Participants
|
19.0 participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 Expression Status
0
|
2 participants
n=5 Participants
|
27 participants
n=7 Participants
|
29.0 participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 Expression Status
1+
|
1 participants
n=5 Participants
|
20 participants
n=7 Participants
|
21.0 participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 Expression Status
2+
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6.0 participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 Expression Status
3+
|
1 participants
n=5 Participants
|
9 participants
n=7 Participants
|
10.0 participants
n=5 Participants
|
|
Human Epidermal Growth Factor Receptor 2 Expression Status
Unknown
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2.0 participants
n=5 Participants
|
|
Presence of Estrogen Hormone Receptor
None
|
4 participants
n=5 Participants
|
25 participants
n=7 Participants
|
29.0 participants
n=5 Participants
|
|
Presence of Estrogen Hormone Receptor
Present
|
2 participants
n=5 Participants
|
37 participants
n=7 Participants
|
39.0 participants
n=5 Participants
|
|
Presence of Estrogen Hormone Receptor
Unknown
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0.0 participants
n=5 Participants
|
|
Presence of Metastasis
None
|
0 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5.0 participants
n=5 Participants
|
|
Presence of Metastasis
Lung
|
0 participants
n=5 Participants
|
27 participants
n=7 Participants
|
27.0 participants
n=5 Participants
|
|
Presence of Metastasis
Bone
|
1 participants
n=5 Participants
|
24 participants
n=7 Participants
|
25.0 participants
n=5 Participants
|
|
Presence of Metastasis
Liver
|
2 participants
n=5 Participants
|
25 participants
n=7 Participants
|
27.0 participants
n=5 Participants
|
|
Presence of Metastasis
Brain
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0.0 participants
n=5 Participants
|
|
Presence of Metastasis
Lymph Node
|
2 participants
n=5 Participants
|
23 participants
n=7 Participants
|
25.0 participants
n=5 Participants
|
|
Presence of Metastasis
Skin
|
1 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7.0 participants
n=5 Participants
|
|
Presence of Metastasis
Other Sites
|
0 participants
n=5 Participants
|
13 participants
n=7 Participants
|
13.0 participants
n=5 Participants
|
|
Presence of Progesterone Hormone Receptor
None
|
3 participant
n=5 Participants
|
39 participant
n=7 Participants
|
42.0 participant
n=5 Participants
|
|
Presence of Progesterone Hormone Receptor
Present
|
2 participant
n=5 Participants
|
23 participant
n=7 Participants
|
25.0 participant
n=5 Participants
|
|
Presence of Progesterone Hormone Receptor
Unknown
|
1 participant
n=5 Participants
|
0 participant
n=7 Participants
|
1.0 participant
n=5 Participants
|
|
Time of Latest Chemotherapy Completion
<3 months
|
2 participants
n=5 Participants
|
40 participants
n=7 Participants
|
42.0 participants
n=5 Participants
|
|
Time of Latest Chemotherapy Completion
≥3 months and <6 months
|
1 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7.0 participants
n=5 Participants
|
|
Time of Latest Chemotherapy Completion
≥6 months and <1 year
|
3 participants
n=5 Participants
|
9 participants
n=7 Participants
|
12.0 participants
n=5 Participants
|
|
Time of Latest Chemotherapy Completion
≥1 year and <2 years
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3.0 participants
n=5 Participants
|
|
Time of Latest Chemotherapy Completion
≥2 years and <3 years
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2.0 participants
n=5 Participants
|
|
Time of Latest Chemotherapy Completion
≥3 years before
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2.0 participants
n=5 Participants
|
|
Time to Recurrence
<1 year
|
4 participants
n=5 Participants
|
22 participants
n=7 Participants
|
26.0 participants
n=5 Participants
|
|
Time to Recurrence
≥1 year and <2 years
|
0 participants
n=5 Participants
|
18 participants
n=7 Participants
|
18.0 participants
n=5 Participants
|
|
Time to Recurrence
≥2 years and <3 years
|
0 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4.0 participants
n=5 Participants
|
|
Time to Recurrence
≥3 years and <4 years
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2.0 participants
n=5 Participants
|
|
Time to Recurrence
≥4 years and < 5 years
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2.0 participants
n=5 Participants
|
|
Time to Recurrence
≥5 to <10 years
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
5.0 participants
n=5 Participants
|
|
Time to Recurrence
No Recurrence
|
1 participants
n=5 Participants
|
10 participants
n=7 Participants
|
11.0 participants
n=5 Participants
|
|
Height
|
152.45 centimeters
STANDARD_DEVIATION 4.05 • n=5 Participants
|
156.43 centimeters
STANDARD_DEVIATION 6.04 • n=7 Participants
|
156.08 centimeters
STANDARD_DEVIATION 5.98 • n=5 Participants
|
|
Weight
|
47.73 kilograms
STANDARD_DEVIATION 1.46 • n=5 Participants
|
57.02 kilograms
STANDARD_DEVIATION 9.15 • n=7 Participants
|
56.20 kilograms
STANDARD_DEVIATION 9.13 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to measured progressive diseaseBest 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.
Outcome measures
| Measure |
Dose Level 1
n=6 Participants
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
n=62 Participants
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Tumor Response
Complete Response
|
0 participants
|
1 participants
|
|
Tumor Response
Progressive Disease
|
2 participants
|
32 participants
|
|
Tumor Response
Not Evaluable
|
2 participants
|
5 participants
|
|
Tumor Response
Partial Response
|
0 participants
|
4 participants
|
|
Tumor Response
Long Stable Disease
|
1 participants
|
4 participants
|
|
Tumor Response
Stable Disease
|
1 participants
|
16 participants
|
SECONDARY outcome
Timeframe: time of response to progressive diseasePopulation: The 5 responding participants (complete response and partial response) at Dose Level 2.
For responders, the minimum and maximum of the duration of complete response, duration of partial response, and duration of overall response were summarized, and the median of response duration and its 95% confidence interval were calculated using the Kaplan-Meier estimation.
Outcome measures
| Measure |
Dose Level 1
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
n=5 Participants
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Duration of Response
|
—
|
10.07 months
Interval 5.43 to 13.8
|
SECONDARY outcome
Timeframe: baseline to measured progressive diseaseTime from study enrollment to first date of disease progression. Time to disease progression was censored at date of death if death was due to other cause. The minimum and maximum of this parameter were summarized, and the median time to progression and its 95% confidence interval were calculated using the Kaplan-Meier estimation.
Outcome measures
| Measure |
Dose Level 1
n=6 Participants
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
n=62 Participants
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Time to Progressive Disease
|
137 days
Interval 97.0 to 196.0
|
92 days
Interval 78.0 to 121.0
|
SECONDARY outcome
Timeframe: baseline to date of death from any cause, evaluate at 1 yearResults are reported as number of participants alive at one year.
Outcome measures
| Measure |
Dose Level 1
n=6 Participants
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
n=62 Participants
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Survival at 1 Year
|
4 participants
|
42 participants
|
SECONDARY outcome
Timeframe: cycle 1Population: Pharmacokinetic data were available from 12 patients.
maximum gemcitabine plasma concentration normalized to 1250 milligrams per square meter of gemcitabine.
Outcome measures
| Measure |
Dose Level 1
n=12 Participants
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Pharmacokinetics - Normalized Cmax
|
29,036 nanograms per milliliter (ng/mL)
|
—
|
SECONDARY outcome
Timeframe: cycle 1Population: Pharmacokinetic data were available on 12 participants.
Area under the gemcitabine plasma concentration-time curve from time zero to infinity. Gemcitabine dose was normalized to 1250 milligrams per square meter.
Outcome measures
| Measure |
Dose Level 1
n=12 Participants
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Pharmacokinetics - Normalized Area Under the Curve
|
15,999 nanograms times hour per milliliter
|
—
|
Adverse Events
Dose Level 1
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Dose Level 2
Serious events: 10 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Level 1
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
1/6 • Number of events 1
|
0.00%
0/62
|
|
Infections and infestations
Cellulitis
|
16.7%
1/6 • Number of events 1
|
1.6%
1/62 • Number of events 1
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Surgical and medical procedures
Catheterisation venous
|
0.00%
0/6
|
3.2%
2/62 • Number of events 2
|
|
Infections and infestations
Infection
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Femur fracture
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Eye disorders
Cataract
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Vascular disorders
Raynaud's phenomenon
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
Other adverse events
| Measure |
Dose Level 1
Gemcitabine at 1000 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
Dose Level 2
Gemcitabine at 1250 mg/m2 administered intravenously over 30 to 60 minutes on Days 1 and 8 in each 3-week (21-day) cycle of study therapy.
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
16.7%
1/6 • Number of events 1
|
12.9%
8/62 • Number of events 8
|
|
Investigations
Neutrophil count decreased
|
33.3%
2/6 • Number of events 2
|
41.9%
26/62 • Number of events 26
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
1/6 • Number of events 1
|
1.6%
1/62 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
4.8%
3/62 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
4.8%
3/62 • Number of events 3
|
|
General disorders
Malaise
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6
|
6.5%
4/62 • Number of events 4
|
|
Investigations
C-reactive protein increased
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Investigations
White blood cell count increased
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
|
Surgical and medical procedures
Tooth extraction
|
0.00%
0/6
|
1.6%
1/62 • Number of events 1
|
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