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

NCT03013504 | Completed Phase 3 DMC

• 1 other identifier: TROIKA
• Study Type: interventional
• Target: 503
• Locations: 12 countries
• Sites: 14

Brief Summary

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.

Conditions

HER2 Positive Breast Cancer

Keywords

randomized; double-blind; parallel group; equivalence; multicentre; phase III; efficacy; safety; pharmacokinetics; HD201; docetaxel; Herceptin; HER2 positive; breast cancer; early breast cancer

Outcome Measures

Primary Outcomes (1)

• total pathological complete response rate (tpCR)

  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.

  After 24 weeks (end of cycle 8)

Secondary Outcomes (10)

• total breast pathological complete response rate (bpCR)

  After 24 weeks (end of cycle 8)

• Overall response rate (ORR)

  After 24 weeks (end of cycle 8)

• Overall Survival (OS)

  From date of randomisation until death from any cause or two years after End of Treatment, whichever comes first

• Event-free Survival (EFS)

  From date of randomisation until death from any cause or two years after End of Treatment, whichever comes first

• Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)

  From baseline through study completion until 18 months or until death, whichever came first

Study Arms (2)

HD201 in combination with docetaxel

EXPERIMENTAL

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

Drug: HD201; Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide

Herceptin® in combination with docetaxel

ACTIVE COMPARATOR

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

Drug: Herceptin; Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide

Interventions

HD201 DRUG

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

Also known as: Trastuzumab

HD201 in combination with docetaxel

Herceptin DRUG

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

Also known as: Trastuzumab

Herceptin® in combination with docetaxel

Docetaxel DRUG

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

HD201 in combination with docetaxel; Herceptin® in combination with docetaxel

Epirubicin DRUG

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

HD201 in combination with docetaxel; Herceptin® in combination with docetaxel

Cyclophosphamide DRUG

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

HD201 in combination with docetaxel; Herceptin® in combination with docetaxel

Eligibility Criteria

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

You may qualify if:

• Able and willing to give written informed consent.
• Females ≥ 18 years of Age
• Eastern Cooperative Oncology Group (ECOG) performance Status (PS) \< 2.
• Known Hormone receptor (oestrogen receptor and progesterone receptor) status.
• HER2 overexpressed as assessed by
• Immunohistochemistry (IHC) or
• Fluorescent in situ hybridisation (FISH); FISH positive is defined as FISH amplification Ratio ≥ 2.0 / number of HER2 gene copies per cell \>2
• Chromogenetic in stu hybridisation (CISH) positive
• Patients with IHC score 3+ or positive FISH/CISH test
• Patients with an IHC score 2+ must also have a positive FISH/CISH test
• LVEF ≥ 50% or within the normal Level of the Institution, as assessed by echocardiography or MUGA scan.
• Life expectancy \> 12 weeks.
• Adequate bone marrow function as evidenced by the following:
• Absolute neutrophils count ≥ 1,500/μL
• Haemoglobin ≥ 9 g/dL

You may not qualify if:

• Patients meeting any of the following criteria must not be enrolled in the study:
• Metastatic (stage IV) with exception of supraclavicular nodes.
• Bilateral breast cancer
• Multicentric breast cancer
• History of any prior invasive breast carcinoma, except for subjects with a past history of ductal carcinoma in situ (DCIS) treated with surgery.
• History of malignant neoplasms within 5 years prior to randomisation, except for curatively treated carcinoma in situ of uterine cervix, basal cell carcinoma of the skin or squamous cell carcinoma of the skin (malignant neoplasms occurring more than 5 years prior to randomisation are permitted if curatively treated with surgery only).
• Previous history of radiation therapy, anti-neoplastic immunotherapy, chemotherapy or anti-neoplastic biotherapy (including prior HER2 directed therapy).
• Major surgery within 2 weeks prior to randomisation
• Serious cardiac illness that would preclude the use of trastuzumab such as:
• history of documented congestive heart failure (CHF) (New York Heart Association, NYHA, class III or greater heart disease)
• LVEF \< 50% by echocardiography or MUGA scan
• angina pectoris requiring anti-anginal medication
• evidence of transmural infarction on electrocardiogram (ECG)
• uncontrolled hypertension (systolic \> 180 mmHg and/or diastolic \> 100 mmHg)
• clinically significant valvular heart disease

Sponsors & Collaborators

• Prestige Biopharma Limited: lead

Study Sites (15)

Minsk Clinical Oncological Dispensary

Minsk, 220013, Belarus

Location

Complex Oncology Center

Plovdiv, 4002, Bulgaria

Location

East Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

Centre René Huguenin (Institut Curie)

Saint-Cloud, 92210, France

Location

S. Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

University of Debrecen

Debrecen, 4032, Hungary

Location

Modena Hospital

Modena, 41124, Italy

Location

Beacon International Specialist Centre

Kuala Lumpur, 46050, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

Szpital Specjalistyczny Brzeziny

Brzeziny, 95-060, Poland

Location

LLC "Vitamed"

Moscow, 129515, Russia

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

GI "V. T. Zaycev Institute General and Urgent Surgery of NAMS of Ukraine "

Kharkiv, 61018, Ukraine

Location

Related Publications (2)

• Pivot X, Manikhas AG, Shamrai V, Dzagnidze G, Soo Hoo HF, Kaewkangsadan V, Petrelli F, Villanueva C, Kim J, Pradhan S, Jaison L, Feyaerts P, Kaufman L, Derde MP, Deforce F, Cox DG. Final analysis of the phase 3 randomized clinical trial comparing HD201 vs. referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting. BMC Cancer. 2023 Jan 31;23(1):112. doi: 10.1186/s12885-023-10574-2.

  PMID: 36721174 DERIVED

• Pivot X, Georgievich MA, Shamrai V, Dzagnidze G, Soo Hoo HF, Kaewkangsadan V, Petrelli F, Villanueva C, Nikolaevich LO, Hii J, Kim J, Pradhan S, Jaison L, Feyaerts P, Kaufman L, Derde MP, Bonamy GMC, Deforce F, Cox DG. Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 May 1;8(5):698-705. doi: 10.1001/jamaoncol.2021.8171.

  PMID: 35238873 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Docetaxel; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2016
• First Posted: January 6, 2017
• Study Start: February 19, 2018
• Primary Completion: April 19, 2019
• Study Completion: January 13, 2022
• Last Updated: November 6, 2024

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1); IT (1); GE (1); BE (1); PL (1); TH (1); HU (2); FR (1); UA (1); ES (1); MY (2); RU (1)