Breast Cancer
Conditions
Brief summary
This is a prospective, Phase IV, multi-center, single arm, open-label, interventional study to evaluate the safety of trastuzumab for the treatment of human epidermal growth factor receptor 2 protein (HER2)-positive node positive or high risk node negative breast cancer participants with regimen consisting of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel (AC-TH Regimen) or a regimen consisting of docetaxel and carboplatin (TCH Regimen) in Indian population.
Interventions
DRUGCarboplatin
TCH regimen: Carboplatin dose = Target Area Under Curve (AUC) (6 milligrams\*milliliter/minute \[mg\*mL/min\]) multiplied by (Glomerular Filtration Rate \[GFR\] + 25). Carboplatin will be administered as IV bolus every 3 weeks for 6 cycles (Cycles 1 to 6).
DRUGCyclophosphamide
AC-TH regimen: Cyclophosphamide 600 mg/m\^2 IV bolus every 3 weeks for 4 cycles (Cycles 1 to 4).
DRUGDocetaxel
AC-TH regimen: Docetaxel 100 mg/m\^2 IV infusion every 3 weeks for 4 cycles (Cycles 5 to 8). TCH regimen: Docetaxel 75 mg/m\^2 IV bolus every 3 weeks for 6 cycles (Cycles 1 to 6).
DRUGDoxorubicin
Participants will receive Doxorubicin 60 mg/m\^2 administered as I.V. bolus injection over 5 to 15 minute every 3 weeks for 4 cycles for AC-TH regimen.
DRUGPaclitaxel
AC-TH regimen: Paclitaxel 175 mg/m\^2 IV infusion every 3 weeks for 4 cycles (Cycles 5 to 8).
DRUGTrastuzumab
AC-TH regimen: For weekly administration, 4 milligrams per kilograms (mg/kg) loading dose on Day 1 of Cycle 5, followed by 2 mg/kg on Day 8 of Cycle 5 and 2 mg/kg every week for 4 cycles (up to Cycle 8). For 3 weekly administration, 8 mg/kg loading dose on Day 1 of Cycle 5, followed by 6 mg/kg every 3 for 4 cycles (up to Cycle 8). From Day 1 of Cycle 9, 6 mg/kg will be administered every 3 weeks up to Cycle 22. TCH regimen: For weekly administration, 4 mg/kg loading dose followed by 2 mg/kg weekly from Cycles 1 to Cycle 6. For 3 weekly administration, 8 mg/kg loading dose followed 6 mg/kg every 3 weeks from Cycles 1 to 6. From Cycle 7, 6 mg/kg every 3 weeks up to Cycle 18. All administrations will be intravenous (IV) infusion.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed early invasive HER2 positive, node positive or high risk node negative breast cancer with no evidence of residual, locally recurrent or metastatic disease and defined as clinical stage I to IIIA that is eligible for adjuvant treatment with trastuzumab * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * HER2 over expression/amplification defined as either Immunohistochemistry (IHC)3+, or IHC2+ and Fluorescence in situ Hybridization (FISH) positive as determined in a central laboratory * At time of starting trastuzumab therapy, LVEF measured by echocardiography * Screening LVEF greater than or equal to (\>/=) 55 percent (%) * Adequate bone marrow, renal, and hepatic function * Agreement to use an adequate, non-hormonal means of contraception by women of childbearing potential
Exclusion criteria
* Any contraindication to trastuzumab * Previous adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent * History of other malignancy, except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies who have been disease-free for at least 5 years * Past history of ductal carcinoma in situ and/or lobular carcinoma that has been treated with any systemic therapy or with radiation therapy to the ipsilateral breast where the invasive cancer subsequently develops * Locally advanced (Stage IIIB and IIIC) and metastatic disease (Stage IV) * Clinically relevant cardiovascular disorder or disease * Uncontrolled hypertension, or history of hypertensive crisis or hypertensive encephalopathy * History of severe allergic or immunological reactions, example difficult to control asthma * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Baseline to every 4 cycles up to Cycle 21 (AC-TH), every 4 cycles up to Cycle 17 (TCH) (each cycle is 21 days), at study treatment completion (12 months post baseline) at 6 month (18 months post baseline) and 12 month follow-up (24 months post baseline) | LVEF assessments were performed every three months (four cycles) using echocardiogram |
| Percentage of Participants With Adverse Events | Baseline up to approximately 5 years and 10 months | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | The date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause within 12 months from the last dose of Trastuzumab for every participant | DFS was defined as time from the date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause. Local, regional or distant recurrence, and contra-lateral breast cancer was assessed by combination of physical examination, mammography and pelvic examination. |
| Overall Survival (OS) | Time from the date of first study treatment until date of death, regardless of the cause of death within 12 months from the last dose of Trastuzumab for every participant. The follow up period was 52 weeks from the last dose of treatment in both arms. | Overall survival was defined as time from the date of first study treatment until date of death, regardless of the cause of death. |
Countries
India
Participant flow
Recruitment details
The study was conducted at 6 investigational sites in India.
Pre-assignment details
Of the 110 participants enrolled, 108 received at least one dose of trastuzumab and were included in the safety population.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab With AC-TH Regimen Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks. | 58 |
| Trastuzumab With TCH Regimen Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks. | 52 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Any other reason which the Investigator deemed participant unsuitable for enrollment into the study | 1 | 0 |
| Overall Study | Disease Progression | 0 | 1 |
| Overall Study | Withdrew Consent | 2 | 1 |
Baseline characteristics
| Characteristic | Trastuzumab With TCH Regimen | Total | Trastuzumab With AC-TH Regimen |
|---|---|---|---|
| Age, Continuous | 51.19 Years STANDARD_DEVIATION 10.94 | 51.59 Years STANDARD_DEVIATION 9.45 | 51.95 Years STANDARD_DEVIATION 7.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 52 Participants | 110 Participants | 58 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 52 Participants | 110 Participants | 58 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 | 1 / 56 | 1 / 52 |
| other Total, other adverse events | 46 / 56 | 51 / 52 |
| serious Total, serious adverse events | 11 / 56 | 9 / 52 |
Outcome results
Primary
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography
LVEF assessments were performed every three months (four cycles) using echocardiogram
Time frame: Baseline to every 4 cycles up to Cycle 21 (AC-TH), every 4 cycles up to Cycle 17 (TCH) (each cycle is 21 days), at study treatment completion (12 months post baseline) at 6 month (18 months post baseline) and 12 month follow-up (24 months post baseline)
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 17 | -1.8 Percentage of LVEF | Standard Deviation 4.77 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 5 | -0.2 Percentage of LVEF | Standard Deviation 4.71 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 21 | -1.8 Percentage of LVEF | Standard Deviation 4.88 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Study Completion Visit | -3.3 Percentage of LVEF | Standard Deviation 6.59 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 9 | -0.5 Percentage of LVEF | Standard Deviation 4.64 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | 6 Month Follow Up | -1.6 Percentage of LVEF | Standard Deviation 5.89 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | 12 Month Follow Up | -2.2 Percentage of LVEF | Standard Deviation 6.28 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 13 | -2.0 Percentage of LVEF | Standard Deviation 6.94 |
| Trastuzumab With AC-TH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Baseline | 60.1 Percentage of LVEF | Standard Deviation 6.17 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | 12 Month Follow Up | -0.4 Percentage of LVEF | Standard Deviation 2.92 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 5 | -0.4 Percentage of LVEF | Standard Deviation 2.72 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | 6 Month Follow Up | -0.3 Percentage of LVEF | Standard Deviation 3.18 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 9 | -1.0 Percentage of LVEF | Standard Deviation 2.98 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 13 | -1.0 Percentage of LVEF | Standard Deviation 2.36 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Cycle 17 | -1.1 Percentage of LVEF | Standard Deviation 3.15 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Study Completion Visit | -0.7 Percentage of LVEF | Standard Deviation 2.72 |
| Trastuzumab With TCH Regimen | Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography | Baseline | 62.1 Percentage of LVEF | Standard Deviation 2.3 |
Primary
Percentage of Participants With Adverse Events
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events.
Time frame: Baseline up to approximately 5 years and 10 months
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab With AC-TH Regimen | Percentage of Participants With Adverse Events | 46 Participants |
| Trastuzumab With TCH Regimen | Percentage of Participants With Adverse Events | 51 Participants |
Secondary
Disease Free Survival (DFS)
DFS was defined as time from the date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause. Local, regional or distant recurrence, and contra-lateral breast cancer was assessed by combination of physical examination, mammography and pelvic examination.
Time frame: The date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause within 12 months from the last dose of Trastuzumab for every participant
Population: ITT population included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab With AC-TH Regimen | Disease Free Survival (DFS) | NA Months |
| Trastuzumab With TCH Regimen | Disease Free Survival (DFS) | NA Months |
Secondary
Overall Survival (OS)
Overall survival was defined as time from the date of first study treatment until date of death, regardless of the cause of death.
Time frame: Time from the date of first study treatment until date of death, regardless of the cause of death within 12 months from the last dose of Trastuzumab for every participant. The follow up period was 52 weeks from the last dose of treatment in both arms.
Population: ITT population included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab With AC-TH Regimen | Overall Survival (OS) | NA Months |
| Trastuzumab With TCH Regimen | Overall Survival (OS) | NA Months |