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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02419742
• Other study ID #: ML28714
• Status: Completed
• Phase: Phase 4
• Start date: August 18, 2015
• Est. completion date: June 24, 2021

Study information

• Verified date: September 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: June 24, 2021
• Est. primary completion date: June 24, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Carboplatin
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).
• Cyclophosphamide
AC-TH regimen: Cyclophosphamide 600 mg/m^2 IV bolus every 3 weeks for 4 cycles (Cycles 1 to 4).
• Docetaxel
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).
• Doxorubicin
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.
• Paclitaxel
AC-TH regimen: Paclitaxel 175 mg/m^2 IV infusion every 3 weeks for 4 cycles (Cycles 5 to 8).
• Trastuzumab
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.

Locations

Country	Name	City	State
India	Manipal Hospital; Department of Oncology	Bangalore	Karnataka
India	MAX Balaji Hospital	Delhi
India	Yashoda Hospital	Hyderabad	Andhra Pradesh
India	Rajiv Gandhi Cancer Institute & Research Center	New Delhi	Delhi
India	Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room	Pune	Maharashtra
India	Dr. GVN Cancer Institute; Medical Oncology	Trichy

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	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)
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.	Baseline up to approximately 5 years and 10 months
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.	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
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 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.