Metastatic Breast Cancer
Conditions
Brief summary
To investigate efficacy, safety and PK of gemcitabine and paclitaxel combination in patients with metastatic breast cancer after adjuvant/neo-adjuvant chemotherapy with anthracycline regimen
Interventions
DRUGgemcitabine
Phase 1: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles (dose escalation) Phase 2: dose determined by phase 1
DRUGpaclitaxel
Phase 1: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles Phase 2: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles
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 adjuvant/neo-adjuvant chemotherapy for breast cancer with anthracycline regimen * To have at least one measurable region * Eastern Cooperative Oncology Group (ECOG) Performance Status: 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 breast cancer * Within 28 days after the latest chemotherapy or radiotherapy, 14 days after the latest hormonal/immunotherapy or 7 days after surgery * To have brain metastases with symptoms * To have severe complication (cardiac infarction, infection, drug hypersensitivity 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. Responders are patients with complete response or partial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progressive Disease | baseline to measured progressive disease | 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. |
| Number of Participants Alive at One Year (1-Year Survival) | baseline to date of death from any cause, evaluated at 1 year | — |
| Duration of Response | time of response to progressive disease | 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. |
| Pharmacokinetics - Area Under the Concentration Curve (AUC) | cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes) | Area under the concentration curve from time zero to infinity. |
| Pharmacokinetics - Half Life (t½) | cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes) | Apparent elimination half-life. |
| Pharmacokinetics - Maximum Plasma Concentration (Cmax) | cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes) | Maximum plasma concentration of gemcitabine plus paclitaxel on Day 1, Cycle 1, and gemcitabine monotherapy on Day 8, Cycle 1. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 Gemcitabine: 1000 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles | 6 |
| Dose Level 2 Gemcitabine: 1250 mg/m2, intravenous (IV), day 1 and day 8 x 2 cycles Paclitaxcel: 175 mg/m2, intravenous (IV), every 21 days x 2 cycles | 56 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Criteria for Starting Next Cycle Not Met | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 3 |
| Overall Study | Patient Condition Aggrevated | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive Disease | 2 | 24 |
| Overall Study | Toxicity | 1 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Total | Dose Level 1 | Dose Level 2 |
|---|---|---|---|
| Age at Primary Diagnosis 30 to <40 years old | 3 participants | 0 participants | 3 participants |
| Age at Primary Diagnosis <30 years old | 0 participants | 0 participants | 0 participants |
| Age at Primary Diagnosis 40 to <50 years old | 21 participants | 1 participants | 20 participants |
| Age at Primary Diagnosis 50 to <60 years old | 27 participants | 3 participants | 24 participants |
| Age at Primary Diagnosis 60 to <70 years old | 10 participants | 2 participants | 8 participants |
| Age at Primary Diagnosis ≥70 years old | 1 participants | 0 participants | 1 participants |
| Age Continuous | 54.7 years STANDARD_DEVIATION 8.46 | 58.2 years STANDARD_DEVIATION 4.49 | 54.4 years STANDARD_DEVIATION 8.73 |
| Body Weight | 55.90 kilograms STANDARD_DEVIATION 9.375 | 57.18 kilograms STANDARD_DEVIATION 15.313 | 55.76 kilograms STANDARD_DEVIATION 8.715 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully Active | 54 participants | 4 participants | 50 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 8 participants | 2 participants | 6 participants |
| Height | 154.60 centimeters STANDARD_DEVIATION 6.312 | 153.53 centimeters STANDARD_DEVIATION 7.987 | 154.71 centimeters STANDARD_DEVIATION 6.184 |
| Region of Enrollment Japan | 62 participants | 6 participants | 56 participants |
| Sex: Female, Male Female | 62 Participants | 6 Participants | 56 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / — | 56 / — |
| serious Total, serious adverse events | 1 / — | 3 / — |
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. Responders are patients with complete response or partial response.
Time frame: baseline to measured progressive disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level 1 | Tumor Response | Partial Response | 3 participants |
| Dose Level 1 | Tumor Response | Progressive Disease | 1 participants |
| Dose Level 1 | Tumor Response | Stable Disease | 1 participants |
| Dose Level 1 | Tumor Response | Not Evaluable | 1 participants |
| Dose Level 1 | Tumor Response | Complete Response | 0 participants |
| Dose Level 2 | Tumor Response | Not Evaluable | 3 participants |
| Dose Level 2 | Tumor Response | Complete Response | 0 participants |
| Dose Level 2 | Tumor Response | Partial Response | 25 participants |
| Dose Level 2 | Tumor Response | Stable Disease | 17 participants |
| Dose Level 2 | Tumor Response | Progressive Disease | 11 participants |
p-value: 0.169t-test, 2 sided
p-value: 0.001t-test, 2 sided
Secondary
Duration of Response
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.
Time frame: time of response to progressive disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 1 | Duration of Response | 4.70 months |
Secondary
Number of Participants Alive at One Year (1-Year Survival)
Time frame: baseline to date of death from any cause, evaluated at 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 | Number of Participants Alive at One Year (1-Year Survival) | 5 participants |
| Dose Level 2 | Number of Participants Alive at One Year (1-Year Survival) | 45 participants |
Secondary
Pharmacokinetics - Area Under the Concentration Curve (AUC)
Area under the concentration curve from time zero to infinity.
Time frame: cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes)
Population: Six participants from each dose level (Dose Level 1 and Dose Level 2) were assessed for pharmacokinetic variables.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level 1 | Pharmacokinetics - Area Under the Concentration Curve (AUC) | 16300 nanograms*hour per milliliter (ng*hr/mL) |
| Dose Level 2 | Pharmacokinetics - Area Under the Concentration Curve (AUC) | 14700 nanograms*hour per milliliter (ng*hr/mL) |
Secondary
Pharmacokinetics - Half Life (t½)
Apparent elimination half-life.
Time frame: cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes)
Population: Six participants from each dose level (Dose Level 1 and Dose Level 2) were assessed for pharmacokinetic variables.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level 1 | Pharmacokinetics - Half Life (t½) | 0.282 hours |
| Dose Level 2 | Pharmacokinetics - Half Life (t½) | 0.258 hours |
Secondary
Pharmacokinetics - Maximum Plasma Concentration (Cmax)
Maximum plasma concentration of gemcitabine plus paclitaxel on Day 1, Cycle 1, and gemcitabine monotherapy on Day 8, Cycle 1.
Time frame: cycle 1, day 1 (0 minutes, 3, 3.25, 3.5, 3.58, 3.75, 4, 4.5, 5 hours) and 8 (0, 15, 30, 35, 45, 60, 90, 120 minutes)
Population: Six participants from each dose level (Dose Level 1 and Dose Level 2) were assessed for pharmacokinetic variables.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dose Level 1 | Pharmacokinetics - Maximum Plasma Concentration (Cmax) | 25800 nanograms per milliliter (ng/mL) |
| Dose Level 2 | Pharmacokinetics - Maximum Plasma Concentration (Cmax) | 25400 nanograms per milliliter (ng/mL) |
Secondary
Time to Progressive Disease
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.
Time frame: baseline to measured progressive disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 1 | Time to Progressive Disease | 310.5 days |
| Dose Level 2 | Time to Progressive Disease | 194.0 days |