Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Trastuzumab

Cyclophosphamide

Docetaxel

Epirubicin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

8 mg/kg i.v. loading dose over 90 mins in Cycle 1 and 6 mg/kg i.v. dose every 3 weeks over 60 mins then 30 mins for subsequent cycles (cycles 2-8), followed by surgery, then adjuvant period of 8mg/kg i.v. loading dose over 90 mins in cycle 9, and subsequent 6mg/kg (if therapy is missed by \>1 week, a re-loading dose of 8mg/kg should be given) over 30 mins for subsequent 9 cycles (cycles 10-18), disease progression, unacceptable toxicity, non-compliance, or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever occurs first.

Neoadjuvant chemotherapy:

Cycles 1-4: Docetaxel 75 mg/m² on day 1 of each 3-weeks cycle via 1h i.v. Infusion Cycles 5-8: EC on day 1 of each 3-weeks cycle: Epirubicin 75 mg/m² via 3-30 mins i.v. Infusion, Cyclophosphamide 500 mg/m² via 3-30 mins i.v. Infusion

8 mg/kg i.v. loading dose over 90 mins in Cycle 1 and 6 mg/kg i.v. dose every 3 weeks over 60 mins then 30 mins for subsequent cycles (cycles 2 -8) for cycles 2-8, followed by surgery, and subsequent adjuvant period of 8mg/kg i.v. loading dose over 90 mins in cycle 9, then 6mg/kg (if therapy is missed by \>1 week, a re-loading dose of 8mg/kg should be given) over 30 mins for subsequent 9 cycles (cycles 10-18), disease progression, unacceptable toxicity, non-compliance, or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever occurs first.

Neoadjuvant chemotherapy:

Cycles 1-4: Docetaxel 75 mg/m² on day 1 of each 3-weeks cycle via 1h i.v. Infusion Cycles 5-8: EC on day 1 of each 3-weeks cycle: Epirubicin 75 mg/m² via 3-30 mins i.v. Infusion, Cyclophosphamide 500 mg/m² via 3-30 mins i.v. Infusion

Loading dose of 8mg/kg in Cycle 1 and 6mg/kg in subsequent cycles.

HD201

Herceptin

75mg/m2 via i.v. infusion during cycles 1 to 4.

75 mg/m2 via i.v. infusion during cycles 5-8.

500 mg/m2 via i.v. infusion during cycles 5-8.

In the TROIKA study, the proposed biosimilar HD201 will be compared to its reference product Herceptin®. The aim of the study is to demonstrate equivalence of HD201 and Herceptin® in terms of efficacy, safety and pharmacokinetics.

This is a randomised, double-blind, parallel group, equivalence, multicentre Phase III study. 500 patients with HER2+ early breast cancer (EBC) will be randomised (1:1) to receive either HD201 in combination with chemotherapy (n=250) or Herceptin® in combination with chemotherapy (n=250).

HD201 or Herceptin® will be administered every 3 weeks for 8 cycles(24 weeks). After administration of the final neoadjuvant study drug dose, surgery will be done within 3-8 weeks followed by an adjuvant treatment period for 10 cycles.

Patients completing the 18 cycles of treatment and those discontinuing the study will attend an End of Treatment (EOT) visit 4 weeks (+/- 2 days), after last administration of study medication, followed by a follow-up period of 2 years.

Patients will attend study visits every 3 weeks. At each visit, patients will undergo a complete physical examination, vital signs, weight, performance status, clinical laboratory tests and adverse events (AEs), concomitant medication will be recorded. After the EOT visit patients will be followed every 6 months for an additional 24 months or until death, whichever occurs first, to collect data on cardiac safety and disease status.

Cardiac safety will be assessed by echocardiography or multigated acquisition (MUGA) scan to evaluate the left ventricular ejection fraction (LVEF) (at screening, before cycle 5, before surgery, before cycles 12 and 16, EOT visit, and at 6 and 12 months after the completion of trastuzumab (more frequent if necessary)) and by means of a 12-lead ECG (at screening, before cycle 5, before surgery, before cycles 12 and 16, EOT visit, and at 6 and 12 months after the completion of trastuzumab).

The primary efficacy endpoint, total pathological complete response (tpCR) will be assessed at the time of surgery after neoadjuvant treatment completion after 24 weeks. tpCR will be assessed both by local and by central reading.

Sampling for pharmacokinetics (PK) analysis (determination of Ctrough values) will be performed in all patients before cycle 5 and cycle 8.

An Independent Data Monitoring Committee will be implemented that reviews accumulating data of the clinical trial with respect to any potential safety issues, study progress and critical efficacy endpoints. The members will be selected on the basis of relevant experience and understanding of clinical research and the issues specific to the therapeutic area, as well as previous data monitoring committee experience.

A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients

A Randomised, Double-blind, Parallel Group, Equivalence, Multicentre Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in Patients With HER2+ Early Breast Cancer

To compare the total pathological complete response rate (tpCR) in patients treated with HD201 plus chemotherapy to that in patients treated with Herceptin® plus chemotherapy.

To compare total breast pathological complete response rate (bpCR) between the two arms at the time of surgery.

ORR defined as proportion of patients whose best overall response is either complete response (CR) or partial response (PR) at the time of surgery.

OS defined as the time from Day 1 of therapy until death from any cause

EFS defined as the time from Day 1 of therapy (day of first infusion of medication on study) until progression of disease or death from any cause.

Safety and tolerability will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and CTC v4.03

Cardiac dysfunction will be monitored by 12-Lead ECG and measurement of the LVEF by echocardiography or MUGA scan

Incidence of human trastuzumab antibodies

Sampling will be performed in all patients to compare the PK through values of HD201 and Herceptin.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients	NCT03013504	HER2 Positive B...	HD201 Herceptin Docetaxel Epirubicin Cyclophosphamid...	18 Years -	Prestige Biopharma Limited
A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients	NCT03013504	HER2 Positive B...	HD201 Herceptin Docetaxel Epirubicin Cyclophosphamid...	18 Years -	Prestige Biopharma Limited

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