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

NCT02419742 | Completed Phase 4 Results FDA Drug

• 1 other identifier: ML28714
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 6

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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

  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)

• 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.

  Baseline up to approximately 5 years and 10 months

Secondary Outcomes (2)

• 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

• 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.

Study Arms (1)

Trastuzumab

EXPERIMENTAL

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.

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

Interventions

Carboplatin DRUG

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).

Trastuzumab

Cyclophosphamide DRUG

AC-TH regimen: Cyclophosphamide 600 mg/m\^2 IV bolus every 3 weeks for 4 cycles (Cycles 1 to 4).

Trastuzumab

Docetaxel DRUG

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).

Trastuzumab

Doxorubicin DRUG

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.

Trastuzumab

Paclitaxel DRUG

AC-TH regimen: Paclitaxel 175 mg/m\^2 IV infusion every 3 weeks for 4 cycles (Cycles 5 to 8).

Trastuzumab

Trastuzumab DRUG

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.

Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

Yashoda Hospital

Hyderabad, Andhra Pradesh, 500082, India

Location

Manipal Hospital; Department of Oncology

Bangalore, Karnataka, 560017, India

Location

Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room

Pune, Maharashtra, 411001, India

Location

Rajiv Gandhi Cancer Institute & Research Center

New Delhi, National Capital Territory of Delhi, 110085, India

Location

MAX Balaji Hospital

Delhi, 110092, India

Location

Dr. GVN Cancer Institute; Medical Oncology

Trichy, 620008, India

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Cyclophosphamide; Docetaxel; Doxorubicin; Paclitaxel; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Anil Kukreja, MD

  Roche Products (India) Pvt. Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: April 17, 2015
• Study Start: August 18, 2015
• Primary Completion: June 24, 2021
• Study Completion: June 24, 2021
• Last Updated: October 12, 2022
• Results First Posted: October 12, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (6)