Breast Cancer
Conditions
Brief summary
The purposes of this study are to determine the safety of gemcitabine and paraplatin either with or without trastuzumab Any side effects that might be associated with these compounds. Whether the two or three drugs listed above when given in combination can help patients with metastatic breast cancer. How long the treatment will stop the growth of the cancer.
Interventions
DRUGGemcitabine
Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion)
DRUGCarboplatin
Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion).
DRUGHerceptin
Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion).
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of metastatic breast cancer 2. Able to visit the doctor's office at least every 14 days during the actual treatment 3. Able to care for yourself, even if you cannot work or participate in other normal activities 4. Your blood results must be adequate for therapy. 5. If you are a female of childbearing potential and test negative for pregnancy, use a reliable method of birth control during and for three months following the last dose of study drug.
Exclusion criteria
1. Have received gemcitabine, paraplatin, or trastuzumab for your cancer. 2. Be pregnant or breastfeeding 3. Have cancer to the brain and has not been treated 4. Have another active cancer besides breast cancer 5. Have received stem cell or bone marrow transplant for hematologic (blood type) cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response | baseline to disease progression/recurrence (up to 3.5 years) | Response using Response Evaluation Criteria In Solid Tumors (RECIST) 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | date of response (CR or PR) until the first date of documented progression or death from any cause (up to 3.5 years) | Among tumor responders, the duration of tumor response is measured from the date of response (complete response \[CR\] or partial response \[PR\]) until the first date of documented progression or death from any cause. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed. |
| Number of Patients Who Experienced Alopecia | Baseline to 3.5 years | — |
| Time to Disease Progression (TTP) | randomization date to the earliest date of the first documented disease progression date or the date of death if the patient dies due to study disease (up to 3.5 years) | If a patient is lost to follow-up, the patient will be censored as of the last date of contact. Patients who start a new treatment before they progress will be censored as of the date of start of the new treatment. If a patient died due to reason other than study disease, and patient has not progressed or received any new treatment, TTP is censored at the date of death. |
| Percentage of Patients With Overall Survival at 1 Year and 2 Years | 1 Year, 2 Years | Kaplan-Meier estimates of overall survival (percentage of patients surviving) at 1 year and 2 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HER2+ Human Epidermal growth factor Receptor 2 positive: Gemcitabine + Carboplatin + Herceptin.
Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion); Herceptin: Day 1 of 14 day cycle (Cycle 1): 8 milligrams per kilogram (mg/kg) intravenous (IV) (90 minute infusion). Day 1 of 14 day cycle (Cycles 2-9): 4 mg/kg IV (30 minute infusion). Day 1 of 21 day cycle (Cycles 10+): 6 mg/kg IV (30 minute infusion). | 50 |
| HER2- (Taxane-) Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-naive patients).
Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion). | 51 |
| HER2- (Taxane+) Human Epidermal growth factor Receptor 2 negative: Gemcitabine + Carboplatin. (Taxane-pretreated patients).
Gemcitabine: Day 1 of 14 day cycle (Cycles 1-9):1500 milligram per square meter (mg/m2) intravenous (IV) (30 minute infusion); Carboplatin: Day 1 of 14 day cycle (Cycles 1-9): Carboplatin area under the curve (AUC)=2.5 intravenous (IV) (30-60 minute infusion). | 49 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Ineligible | 0 | 1 | 0 |
| Overall Study | Physician Decision | 2 | 9 | 6 |
| Overall Study | Reason Not Specified | 2 | 1 | 3 |
| Overall Study | Sponsor Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 5 |
Baseline characteristics
| Characteristic | HER2+ | HER2- (Taxane-) | HER2- (Taxane+) | Total |
|---|---|---|---|---|
| Age Continuous | 56.1 years STANDARD_DEVIATION 9.45 | 55.7 years STANDARD_DEVIATION 11.17 | 54.8 years STANDARD_DEVIATION 9.92 | 55.55 years STANDARD_DEVIATION 10.16 |
| Eastern Cooperative Oncology Group Performance Status 0 - Fully Active | 41 participants | 36 participants | 32 participants | 109 participants |
| Eastern Cooperative Oncology Group Performance Status 1 - Ambulatory, Restricted Strenuous Activity | 8 participants | 14 participants | 17 participants | 39 participants |
| Eastern Cooperative Oncology Group Performance Status 2 - Ambulatory, No Work Activities | 1 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity Black | 8 participants | 5 participants | 11 participants | 24 participants |
| Race/Ethnicity Caucasian | 31 participants | 42 participants | 36 participants | 109 participants |
| Race/Ethnicity Hispanic | 7 participants | 4 participants | 1 participants | 12 participants |
| Race/Ethnicity Other | 4 participants | 0 participants | 1 participants | 5 participants |
| Region of Enrollment United States | 50 participants | 51 participants | 49 participants | 150 participants |
| Sex: Female, Male Female | 50 Participants | 51 Participants | 49 Participants | 150 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 50 / 50 | 48 / 48 | 45 / 47 |
| serious Total, serious adverse events | 10 / 50 | 11 / 48 | 10 / 47 |
Outcome results
Primary
Overall Tumor Response
Response using Response Evaluation Criteria In Solid Tumors (RECIST) 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.
Time frame: baseline to disease progression/recurrence (up to 3.5 years)
Population: Efficacy evaluable subjects include all subjects who received at least 2 cycles of treatment with at least 1 follow-up tumor assessment, and did not violate the protocol in any fundamental manner related to the evaluation of efficacy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HER2+ | Overall Tumor Response | Progressive Disease (PD) | 4 participants |
| HER2+ | Overall Tumor Response | Stable Disease (SD) | 12 participants |
| HER2+ | Overall Tumor Response | Complete Response (CR) | 6 participants |
| HER2+ | Overall Tumor Response | Partial Response (PR) | 26 participants |
| HER2+ | Overall Tumor Response | Not Evaluable (NE) | 2 participants |
| HER2- (Taxane-) | Overall Tumor Response | Stable Disease (SD) | 20 participants |
| HER2- (Taxane-) | Overall Tumor Response | Complete Response (CR) | 0 participants |
| HER2- (Taxane-) | Overall Tumor Response | Partial Response (PR) | 13 participants |
| HER2- (Taxane-) | Overall Tumor Response | Progressive Disease (PD) | 12 participants |
| HER2- (Taxane-) | Overall Tumor Response | Not Evaluable (NE) | 2 participants |
| HER2- (Taxane+) | Overall Tumor Response | Not Evaluable (NE) | 1 participants |
| HER2- (Taxane+) | Overall Tumor Response | Progressive Disease (PD) | 17 participants |
| HER2- (Taxane+) | Overall Tumor Response | Complete Response (CR) | 1 participants |
| HER2- (Taxane+) | Overall Tumor Response | Stable Disease (SD) | 13 participants |
| HER2- (Taxane+) | Overall Tumor Response | Partial Response (PR) | 15 participants |
Secondary
Duration of Response
Among tumor responders, the duration of tumor response is measured from the date of response (complete response \[CR\] or partial response \[PR\]) until the first date of documented progression or death from any cause. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed.
Time frame: date of response (CR or PR) until the first date of documented progression or death from any cause (up to 3.5 years)
Population: Number of patients with complete or partial response. Censored patients: 6 in HER2+, 6 in HER2- (Taxane-), and 5 in HER2- (Taxane+).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HER2+ | Duration of Response | 6.9 months |
| HER2- (Taxane-) | Duration of Response | 6.4 months |
| HER2- (Taxane+) | Duration of Response | 5.6 months |
Secondary
Number of Patients Who Experienced Alopecia
Time frame: Baseline to 3.5 years
Population: Number of patients who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2+ | Number of Patients Who Experienced Alopecia | 21 participants |
| HER2- (Taxane-) | Number of Patients Who Experienced Alopecia | 17 participants |
| HER2- (Taxane+) | Number of Patients Who Experienced Alopecia | 16 participants |
Secondary
Percentage of Patients With Overall Survival at 1 Year and 2 Years
Kaplan-Meier estimates of overall survival (percentage of patients surviving) at 1 year and 2 years.
Time frame: 1 Year, 2 Years
Population: Intent to treat population: all randomized patients. Censored patients: 31 HER2+; 19 HER2- (Taxane-); 9 HER2- (Taxane+).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HER2+ | Percentage of Patients With Overall Survival at 1 Year and 2 Years | 1 Year Overall Survival | 90.0 percentage of participants |
| HER2+ | Percentage of Patients With Overall Survival at 1 Year and 2 Years | 2 Year Overall Survival | 73.3 percentage of participants |
| HER2- (Taxane-) | Percentage of Patients With Overall Survival at 1 Year and 2 Years | 1 Year Overall Survival | 67.5 percentage of participants |
| HER2- (Taxane-) | Percentage of Patients With Overall Survival at 1 Year and 2 Years | 2 Year Overall Survival | 41.4 percentage of participants |
| HER2- (Taxane+) | Percentage of Patients With Overall Survival at 1 Year and 2 Years | 1 Year Overall Survival | 47.8 percentage of participants |
| HER2- (Taxane+) | Percentage of Patients With Overall Survival at 1 Year and 2 Years | 2 Year Overall Survival | 20.5 percentage of participants |
Secondary
Time to Disease Progression (TTP)
If a patient is lost to follow-up, the patient will be censored as of the last date of contact. Patients who start a new treatment before they progress will be censored as of the date of start of the new treatment. If a patient died due to reason other than study disease, and patient has not progressed or received any new treatment, TTP is censored at the date of death.
Time frame: randomization date to the earliest date of the first documented disease progression date or the date of death if the patient dies due to study disease (up to 3.5 years)
Population: Intent to treat population: all randomized patients. Censored patients: 10 in HER2+, 20 in HER2- (Taxane-), and 12 in HER2- (Taxane+).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HER2+ | Time to Disease Progression (TTP) | 7.2 months |
| HER2- (Taxane-) | Time to Disease Progression (TTP) | 5.6 months |
| HER2- (Taxane+) | Time to Disease Progression (TTP) | 4.6 months |