Back to resultsSafety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen
Primary Purpose
Breast Cancer
Status
Completed
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Carboplatin
Cyclophosphamide
Docetaxel
Doxorubicin
Paclitaxel
Trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
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
Sites / Locations
- Yashoda Hospital
- Rajiv Gandhi Cancer Institute & Research Center
- Manipal Hospital; Department of Oncology
- Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room
- MAX Balaji Hospital
- Dr. GVN Cancer Institute; Medical Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Trastuzumab
Arm Description
Participants will receive trastuzumab as a part of either AC-TH or TCH treatment regimen. The choice of the regimen will be based on investigator's discretion referring the local prescribing document of trastuzumab. AC-TH consists of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. TCH consists of docetaxel and carboplatin. Trastuzumab will be common in both treatment regimens and could be administered weekly or every 3 weeks, as per investigator discretion. Each cycle will be of 3 weeks.
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02419742
Brief Title
Safety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen
Official Title
An Indian Multicentric Open Label Prospective Phase IV Study to Evaluate Safety and Efficacy of Trastuzumab in Her2 Positive, Node Positive or High Risk Node Negative Breast Cancer as Part of a Treatment Regimen Consisting of Doxorubicin, Cyclophosphamide, With Either Docetaxel or Paclitaxel (AC-TH) or Docetaxel and Carboplatin (TCH)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
August 18, 2015 (Actual)
Primary Completion Date
June 24, 2021 (Actual)
Study Completion Date
June 24, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trastuzumab
Arm Type
Experimental
Arm Description
Participants will receive trastuzumab as a part of either AC-TH or TCH treatment regimen. The choice of the regimen will be based on investigator's discretion referring the local prescribing document of trastuzumab. AC-TH consists of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. TCH consists of docetaxel and carboplatin. Trastuzumab will be common in both treatment regimens and could be administered weekly or every 3 weeks, as per investigator discretion. Each cycle will be of 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
AC-TH regimen: Cyclophosphamide 600 mg/m^2 IV bolus every 3 weeks for 4 cycles (Cycles 1 to 4).
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
AC-TH regimen: Paclitaxel 175 mg/m^2 IV infusion every 3 weeks for 4 cycles (Cycles 5 to 8).
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography
Description
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)
Title
Percentage of Participants With Adverse Events
Description
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
Secondary Outcome Measure Information:
Title
Disease Free Survival (DFS)
Description
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
Title
Overall Survival (OS)
Description
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.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anil Kukreja, MD
Organizational Affiliation
Roche Products (India) Pvt. Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Yashoda Hospital
City
Hyderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500082
Country
India
Facility Name
Rajiv Gandhi Cancer Institute & Research Center
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110085
Country
India
Facility Name
Manipal Hospital; Department of Oncology
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560017
Country
India
Facility Name
Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411001
Country
India
Facility Name
MAX Balaji Hospital
City
Delhi
ZIP/Postal Code
110092
Country
India
Facility Name
Dr. GVN Cancer Institute; Medical Oncology
City
Trichy
ZIP/Postal Code
620008
Country
India
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen
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