Safety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen

Phase 4

Completed

Conditions: Breast Cancer

Interventions: Drug: Carboplatin
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Doxorubicin
Drug: Paclitaxel
Drug: Trastuzumab

Registration Number: NCT02419742

Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 110

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trastuzumab	Doxorubicin	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.
Trastuzumab	Docetaxel	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.
Trastuzumab	Carboplatin	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.
Trastuzumab	Cyclophosphamide	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.
Trastuzumab	Paclitaxel	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.
Trastuzumab	Trastuzumab	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (6): Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room
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Pune, Maharashtra, India
Manipal Hospital; Department of Oncology
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Bangalore, Karnataka, India
MAX Balaji Hospital
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Delhi, India
Yashoda Hospital
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Hyderabad, Andhra Pradesh, India
Dr. GVN Cancer Institute; Medical Oncology
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Trichy, India
Rajiv Gandhi Cancer Institute & Research Center
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New Delhi, Delhi, India