Breast Cancer
Conditions
Brief summary
Gemcitabine and anthracycline combination has shown encouraging activity as neoadjuvant chemotherapy in locally advanced breast cancer. An addition of sequential gemcitabine and cisplatin, also a highly active combination in this indication, may result in improvement in pathological response and overall survival. Patients with operable breast cancer will be treated in neoadjuvant setting with gemcitabine plus doxorubicin, followed by gemcitabine plus cisplatin.
Interventions
DRUGgemcitabine
1200 mg/m\^2, intravenous (IV) day 1 and day 8 every 21 days x 4 cycles (1-4) then 1000 mg/m\^2, IV, day 1 and day 8 every 21 days x 4 cycles (5-8)
DRUGdoxorubicin
60 mg/m\^2, IV, every 21 days x 4 cycles (1-4)
DRUGcisplatin
70 mg/m\^2, IV, every 21 days x 4 cycles (5-8)
PROCEDUREsurgery
Surgery follows 8 cycles of chemotherapy. Extent and type of surgery is guided by tumor size, physician and/or patient decision.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of breast carcinoma * No previous chemotherapy, with bidimensionally measurable locally advanced disease * Adequate performance status (Karnofsky Performance Status \[KPS\] greater than or equal to 70), bone marrow reserves, hepatic, cardiac and renal functions.
Exclusion criteria
* Inflammatory breast cancer * Pregnancy and Breast-feeding * Serious concomitant disorder or infection * Previous cancer within the last 5 years or a second primary malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Pathological Complete Response (Pathological Complete Response Rate) | tumor assessment at baseline and during surgery after eight 21-day treatment cycles | Complete pathological response: No invasive tumor cells identified from sections from site of previous cancer. Require evidence corroborating prior presence of invasive cancer, which requires detection of abnormal fibroelastic breast stroma devoid of normal lobular units and contains foamy macrophages with moderate numbers of fibroblasts and mononuclear inflammatory cells. Presence of nondescript collagenised lobules or breast fibrous tissue is not evidence that tumor site has been adequately sampled and macroscopic assessment and sampling is needed until original neoplastic stroma identified. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Deaths During Study | baseline through last cycle on study drug (eight 21-day cycles) | — |
| Progression Free Survival (PFS) | baseline to measured progressive disease or death from any cause (up to 68 months) | PFS was defined as the date of enrollment to the first date of documented disease progression or death from any cause. Because the median was not reached, results are presented as the Outcome: Number of Participants with Disease Progression or Death at Various Timepoints. |
| Overall Survival | baseline to date of death from any cause up to 68 months | Overall survival was defined as the date of enrollment to the date of death from any cause. Because the median was not reached, results will be presented as the Outcome: Number of Participants who Died from Any Cause at Various Timepoints. |
| Time to Treatment Failure | baseline to stopping treatment (up to 68 months) | Time to treatment failure was defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed. Because the upper limit of the 95% Confidence Interval of median survival was not calculable, results are presented as the Outcome: Number of Participants with Time to Treatment Failure at Various Timepoints. |
| Number of Patients Eligible for Breast Conservation Surgery at Baseline and Number of Patients Undergoing Breast Conservation Surgery | baseline, after eight 21-day cycles of study drug | The extent and type of surgery was guided by the tumor size, physician and/or patient decision. It was either conservation surgery or mastectomy with axillary lymph node dissection. Results are reported on the number of patients who underwent breast conservation surgery. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery Gemcitabine: 1200 mg/m\^2, intravenous (IV) day 1 and day 8 every 21 days x 4 cycles (1-4) then 1000 mg/m\^2, IV, day 1 and day 8 every 21 days x 4 cycles (5-8).
Doxorubicin: 60 mg/m\^2, IV, every 21 days x 4 cycles (1-4). Cisplatin: 70 mg/m\^2, IV, every 21 days x 4 cycles (5-8). Surgery follows 8 cycles of chemotherapy. Extent and type of surgery is guided by tumor size, physician and/or patient decision. | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death - Not Study-Drug Related | 1 |
| Overall Study | Death - Possibly Study Drug Related | 4 |
| Overall Study | Patient/Physician: Satisfactory Response | 4 |
| Overall Study | Patient: Satisfactory Response | 5 |
| Overall Study | Progressive Disease/Lack of Efficacy | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Gemcitabine+Doxorubicin+Cisplatin+Surgery |
|---|---|
| Age Continuous | 46 years |
| Body Surface Area | 1.44 meters squared (m^2) |
| Diagnosis Cytological | 53 participants |
| Diagnosis Histopathological | 12 participants |
| Disease Stage Stage IIA | 3 participants |
| Disease Stage Stage IIB | 30 participants |
| Disease Stage Stage IIIA | 18 participants |
| Disease Stage Stage IIIB | 14 participants |
| Height | 153 centimeters (cm) |
| Hormone Receptor Status ER- / PR- | 25 participants |
| Hormone Receptor Status ER- / PR+ | 3 participants |
| Hormone Receptor Status ER+ / PR- | 8 participants |
| Hormone Receptor Status ER+ / PR+ | 27 participants |
| Hormone Receptor Status No Assessment | 2 participants |
| Human Epidermal Growth Factor Receptor 2 (HER-2) Status 0 | 27 participants |
| Human Epidermal Growth Factor Receptor 2 (HER-2) Status 1+ | 8 participants |
| Human Epidermal Growth Factor Receptor 2 (HER-2) Status 2+ | 2 participants |
| Human Epidermal Growth Factor Receptor 2 (HER-2) Status 3+ | 19 participants |
| Human Epidermal Growth Factor Receptor 2 (HER-2) Status Insufficient Sample | 2 participants |
| Human Epidermal Growth Factor Receptor 2 (HER-2) Status Not Detected | 7 participants |
| Karnofsky Performance Status Scale 100 - Normal no complaints; no evidence of disease | 9 participants |
| Karnofsky Performance Status Scale 90 - Normal activity; minor signs of disease | 56 participants |
| Largest Lesion Size | 30 millimeters (mm) |
| Menopausal Status Postmenopausal | 36 participants |
| Menopausal Status Premenopausal | 29 participants |
| Race/Ethnicity, Customized Indian | 65 participants |
| Region of Enrollment India | 65 participants |
| Sex: Female, Male Female | 65 Participants |
| Sex: Female, Male Male | 0 Participants |
| Weight | 57 kilograms (kg) |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 64 / 65 |
| serious Total, serious adverse events | 17 / 65 |
Outcome results
Primary
Number of Patients With Pathological Complete Response (Pathological Complete Response Rate)
Complete pathological response: No invasive tumor cells identified from sections from site of previous cancer. Require evidence corroborating prior presence of invasive cancer, which requires detection of abnormal fibroelastic breast stroma devoid of normal lobular units and contains foamy macrophages with moderate numbers of fibroblasts and mononuclear inflammatory cells. Presence of nondescript collagenised lobules or breast fibrous tissue is not evidence that tumor site has been adequately sampled and macroscopic assessment and sampling is needed until original neoplastic stroma identified.
Time frame: tumor assessment at baseline and during surgery after eight 21-day treatment cycles
Population: Intent to treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Patients With Pathological Complete Response (Pathological Complete Response Rate) | 13 participants |
Secondary
Number of Patients Eligible for Breast Conservation Surgery at Baseline and Number of Patients Undergoing Breast Conservation Surgery
The extent and type of surgery was guided by the tumor size, physician and/or patient decision. It was either conservation surgery or mastectomy with axillary lymph node dissection. Results are reported on the number of patients who underwent breast conservation surgery.
Time frame: baseline, after eight 21-day cycles of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Patients Eligible for Breast Conservation Surgery at Baseline and Number of Patients Undergoing Breast Conservation Surgery | Eligible for Surgery at Baseline | 0 participiants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Patients Eligible for Breast Conservation Surgery at Baseline and Number of Patients Undergoing Breast Conservation Surgery | Underwent Surgery | 18 participiants |
Secondary
Overall Survival
Overall survival was defined as the date of enrollment to the date of death from any cause. Because the median was not reached, results will be presented as the Outcome: Number of Participants who Died from Any Cause at Various Timepoints.
Time frame: baseline to date of death from any cause up to 68 months
Population: Median was not reached
Secondary
Progression Free Survival (PFS)
PFS was defined as the date of enrollment to the first date of documented disease progression or death from any cause. Because the median was not reached, results are presented as the Outcome: Number of Participants with Disease Progression or Death at Various Timepoints.
Time frame: baseline to measured progressive disease or death from any cause (up to 68 months)
Population: Median was not reached.
Secondary
Summary of Deaths During Study
Time frame: baseline through last cycle on study drug (eight 21-day cycles)
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Summary of Deaths During Study | Study Disease | 0 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Summary of Deaths During Study | Study Drug Toxicity: Cardiac arrest | 1 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Summary of Deaths During Study | Study Drug Toxicity: Infection with neutropenia | 1 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Summary of Deaths During Study | Study Drug Toxicity: Neutropenic sepsis | 2 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Summary of Deaths During Study | Myocardial infarction | 1 participants |
Secondary
Time to Treatment Failure
Time to treatment failure was defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed. Because the upper limit of the 95% Confidence Interval of median survival was not calculable, results are presented as the Outcome: Number of Participants with Time to Treatment Failure at Various Timepoints.
Time frame: baseline to stopping treatment (up to 68 months)
Population: Upper limit of 95% Confidence Interval of median survival was not calculable.
Post Hoc
Number of Participants Who Died From Any Cause at Various Time Points
The cumulative number of participants with an event (death from any cause) are presented at various time points, as well as the number of participants at risk for the event. Participants at risk are the number of participants still alive at the beginning of each time point.
Time frame: baseline up to 68 months
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 48 Months: Number of Patients With Event | 14 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 3 Months: Number of Patients With Event | 3 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 3 Months: Number of Patients at Risk | 60 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 6 Months: Number of Patients With Event | 5 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 6 Months: Number of Patients at Risk | 51 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 12 Months: Number of Patients With Event | 7 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 12 Months: Number of Patients at Risk | 43 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 26 Months: Number of Patients With Event | 11 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 26 Months: Number of Patients at Risk | 37 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 48 Months: Number of Patients at Risk | 24 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 68 Months: Number of Patients With Event | 15 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants Who Died From Any Cause at Various Time Points | 68 Months: Number of Patients at Risk | 1 participants |
Post Hoc
Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study
The cumulative number of participants with an event (either progressive disease or death) are presented at various time points, as well as the number of participants at risk for the event. Participants at risk are the number of participants without progressive disease or still alive at the beginning of each time point.
Time frame: baseline up to 68 months
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 68 Months: Number of Patients with Event | 21 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 3 Months: Number of Patients with Event | 5 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 3 Months: Number of Patients at Risk | 59 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 6 Months: Number of Patients with Event | 8 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 6 Months: Number of Patients at Risk | 50 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 12 Months: Number of Patients with Event | 11 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 12 Months: Number of Patients at Risk | 41 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 24 Months: Number of Patients with Event | 15 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 24 Months: Number of Patients at Risk | 36 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 48 Months: Number of Patients with Event | 21 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 48 Months: Number of Patients at Risk | 23 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Progressive Disease or Death at Various Time Points Throughout the Study | 68 Months: Number of Patients at Risk | 1 participants |
Post Hoc
Number of Participants With Time to Treatment Failure at Various Time Points
This outcome is in place of the time to treatment failure outcome. The cumulative number of participants with an event (disease progression, death as a result of any cause, or early discontinuation of treatment) are presented at various time points, as well as the number of participants at risk for the event. Participants at risk are the number of participants without disease progression, are alive, or did not discontinue treatment early at the beginning of each time point.
Time frame: baseline to stopping treatment (up to 68 months)
Population: Intent to treat population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 48 Months: Number of Patients at Risk | 23 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 68 Months: Number of Patients at Risk | 1 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 3 Months: Number of Patients with Event | 11 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 3 Months: Number of Patients at Risk | 59 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 6 Months: Number of Patients with Event | 19 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 6 Months: Number of Patients at Risk | 50 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 12 Months: Number of Patients with Event | 25 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 12 Months: Number of Patients at Risk | 41 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 24 Months: Number of Patients with Event | 29 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 24 Months: Number of Patients at Risk | 36 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 48 Months: Number of Patients with Event | 35 participants |
| Gemcitabine+Doxorubicin+Cisplatin+Surgery | Number of Participants With Time to Treatment Failure at Various Time Points | 68 Months: Number of Patients with Event | 35 participants |