Metastatic Breast Cancer
Conditions
Keywords
after, anthracycline, taxane, regimen
Brief summary
To investigate efficacy, safety and PK of GEM monotherapy after prior chemotherapy with anthracycline and taxane regimen for patients with metastatic breast cancer
Interventions
DRUGgemcitabine
1000 mg/m2, intravenous (IV), day 1 and day 8 every 21 days
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Histologically and/or cytologically confirmed breast cancer * Received prior chemotherapy for metastatic breast cancer with anthracycline and taxane regimen * To have at least one measurable region * PS: 0-1 * To have adequate organ function (bone marrow, liver and renal function)
Exclusion criteria
* To have Interstitial pneumonia or pulmonary fibrosis * To have inflammatory carcinoma * Within 28 days after the latest chemotherapy or radiotherapy, 14 days after the latest hormonal/immunotherapy or 7 days after surgery * To have brain metastasis with symptom * To have severe complication (cardiac infarction, infection, drug hyper sensitivity or diabetes)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | baseline to measured progressive disease | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | time of response to progressive disease | 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. |
| Time to Progressive Disease | baseline to measured progressive disease | Time 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. |
| Survival at 1 Year | baseline to date of death from any cause, evaluate at 1 year | Results are reported as number of participants alive at one year. |
| Pharmacokinetics - Normalized Cmax | cycle 1 | maximum gemcitabine plasma concentration normalized to 1250 milligrams per square meter of gemcitabine. |
| Pharmacokinetics - Normalized Area Under the Curve | cycle 1 | Area under the gemcitabine plasma concentration-time curve from time zero to infinity. Gemcitabine dose was normalized to 1250 milligrams per square meter. |
Countries
Japan
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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. | 62 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Lack of Efficacy | 1 | 5 |
| Overall Study | Pathologic Aggrevation | 0 | 1 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Progression of Disease | 4 | 42 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Dose Level 2 | Dose Level 1 |
|---|---|---|---|
| Age Continuous | 52.5 years STANDARD_DEVIATION 10.93 | 52.4 years STANDARD_DEVIATION 11.25 | 53.3 years STANDARD_DEVIATION 7.45 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully Active | 49.0 participants | 45 participants | 4 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 19.0 participants | 17 participants | 2 participants |
| Height | 156.08 centimeters STANDARD_DEVIATION 5.98 | 156.43 centimeters STANDARD_DEVIATION 6.04 | 152.45 centimeters STANDARD_DEVIATION 4.05 |
| Human Epidermal Growth Factor Receptor 2 Expression Status 0 | 29.0 participants | 27 participants | 2 participants |
| Human Epidermal Growth Factor Receptor 2 Expression Status 1+ | 21.0 participants | 20 participants | 1 participants |
| Human Epidermal Growth Factor Receptor 2 Expression Status 2+ | 6.0 participants | 4 participants | 2 participants |
| Human Epidermal Growth Factor Receptor 2 Expression Status 3+ | 10.0 participants | 9 participants | 1 participants |
| Human Epidermal Growth Factor Receptor 2 Expression Status Unknown | 2.0 participants | 2 participants | 0 participants |
| Presence of Estrogen Hormone Receptor None | 29.0 participants | 25 participants | 4 participants |
| Presence of Estrogen Hormone Receptor Present | 39.0 participants | 37 participants | 2 participants |
| Presence of Estrogen Hormone Receptor Unknown | 0.0 participants | 0 participants | 0 participants |
| Presence of Metastasis Bone | 25.0 participants | 24 participants | 1 participants |
| Presence of Metastasis Brain | 0.0 participants | 0 participants | 0 participants |
| Presence of Metastasis Liver | 27.0 participants | 25 participants | 2 participants |
| Presence of Metastasis Lung | 27.0 participants | 27 participants | 0 participants |
| Presence of Metastasis Lymph Node | 25.0 participants | 23 participants | 2 participants |
| Presence of Metastasis None | 5.0 participants | 5 participants | 0 participants |
| Presence of Metastasis Other Sites | 13.0 participants | 13 participants | 0 participants |
| Presence of Metastasis Skin | 7.0 participants | 6 participants | 1 participants |
| Presence of Progesterone Hormone Receptor None | 42.0 participant | 39 participant | 3 participant |
| Presence of Progesterone Hormone Receptor Present | 25.0 participant | 23 participant | 2 participant |
| Presence of Progesterone Hormone Receptor Unknown | 1.0 participant | 0 participant | 1 participant |
| Region of Enrollment Japan | 68.0 participants | 62 participants | 6 participants |
| Sex: Female, Male Female | 68.0 Participants | 62 Participants | 6 Participants |
| Sex: Female, Male Male | 0.0 Participants | 0 Participants | 0 Participants |
| Time of Latest Chemotherapy Completion ≥1 year and <2 years | 3.0 participants | 3 participants | 0 participants |
| Time of Latest Chemotherapy Completion ≥2 years and <3 years | 2.0 participants | 2 participants | 0 participants |
| Time of Latest Chemotherapy Completion <3 months | 42.0 participants | 40 participants | 2 participants |
| Time of Latest Chemotherapy Completion ≥3 months and <6 months | 7.0 participants | 6 participants | 1 participants |
| Time of Latest Chemotherapy Completion ≥3 years before | 2.0 participants | 2 participants | 0 participants |
| Time of Latest Chemotherapy Completion ≥6 months and <1 year | 12.0 participants | 9 participants | 3 participants |
| Time to Recurrence <1 year | 26.0 participants | 22 participants | 4 participants |
| Time to Recurrence ≥1 year and <2 years | 18.0 participants | 18 participants | 0 participants |
| Time to Recurrence ≥2 years and <3 years | 4.0 participants | 4 participants | 0 participants |
| Time to Recurrence ≥3 years and <4 years | 2.0 participants | 2 participants | 0 participants |
| Time to Recurrence ≥4 years and < 5 years | 2.0 participants | 2 participants | 0 participants |
| Time to Recurrence ≥5 to <10 years | 5.0 participants | 4 participants | 1 participants |
| Time to Recurrence No Recurrence | 11.0 participants | 10 participants | 1 participants |
| Weight | 56.20 kilograms STANDARD_DEVIATION 9.13 | 57.02 kilograms STANDARD_DEVIATION 9.15 | 47.73 kilograms STANDARD_DEVIATION 1.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / — | 34 / — |
| serious Total, serious adverse events | 1 / — | 10 / — |
Outcome results
Primary
Tumor Response
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.
Time frame: baseline to measured progressive disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level 1 | Tumor Response | Complete Response | 0 participants |
| Dose Level 1 | Tumor Response | Partial Response | 0 participants |
| Dose Level 1 | Tumor Response | Long Stable Disease | 1 participants |
| Dose Level 1 | Tumor Response | Stable Disease | 1 participants |
| Dose Level 1 | Tumor Response | Progressive Disease | 2 participants |
| Dose Level 1 | Tumor Response | Not Evaluable | 2 participants |
| Dose Level 2 | Tumor Response | Progressive Disease | 32 participants |
| Dose Level 2 | Tumor Response | Complete Response | 1 participants |
| Dose Level 2 | Tumor Response | Stable Disease | 16 participants |
| Dose Level 2 | Tumor Response | Partial Response | 4 participants |
| Dose Level 2 | Tumor Response | Not Evaluable | 5 participants |
| Dose Level 2 | Tumor Response | Long Stable Disease | 4 participants |
Secondary
Duration of Response
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.
Time frame: time of response to progressive disease
Population: The 5 responding participants (complete response and partial response) at Dose Level 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 2 | Duration of Response | 10.07 months |
Secondary
Pharmacokinetics - Normalized Area Under the Curve
Area under the gemcitabine plasma concentration-time curve from time zero to infinity. Gemcitabine dose was normalized to 1250 milligrams per square meter.
Time frame: cycle 1
Population: Pharmacokinetic data were available on 12 participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level 1 | Pharmacokinetics - Normalized Area Under the Curve | 15,999 nanograms times hour per milliliter |
Secondary
Pharmacokinetics - Normalized Cmax
maximum gemcitabine plasma concentration normalized to 1250 milligrams per square meter of gemcitabine.
Time frame: cycle 1
Population: Pharmacokinetic data were available from 12 patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level 1 | Pharmacokinetics - Normalized Cmax | 29,036 nanograms per milliliter (ng/mL) |
Secondary
Survival at 1 Year
Results are reported as number of participants alive at one year.
Time frame: baseline to date of death from any cause, evaluate at 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 | Survival at 1 Year | 4 participants |
| Dose Level 2 | Survival at 1 Year | 42 participants |
Secondary
Time to Progressive Disease
Time 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.
Time frame: baseline to measured progressive disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 1 | Time to Progressive Disease | 137 days |
| Dose Level 2 | Time to Progressive Disease | 92 days |