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HER2 Positive Breast CancerPhase 3TROIKANCT03013504

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

A Phase 3 study testing HD201, Herceptin and Docetaxel in people with HER2 Positive Breast Cancer, run by Prestige Biopharma Limited at 15 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
HER2 Positive Breast Cancer
What is being tested?
HD201, Herceptin and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
503 participants
Where
15 sitesin 13 countries
Study dates
19 Feb 2018to 13 Jan 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Platelet count ≥ 100,000/μL Up to 5% Deviation is acceptable.
  • Adequate hepatic and renal function as evidenced by the following:
  • Creatinine clearance ≥ 60mL/min
  • total Bilirubin ≤ 1.5x upper limit of normal (ULN)
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN Up to 10% deviation is acceptable.
  • Ability to comply with the study protocol.
  • Female patients of childbearing potential must have a negative Serum pregnancy test within 7 days prior to first dose of study treatment and agree to use effective contraception (intrauterine device, diaphragm, diaphragm with spermicide or a reliable barrier method, eg condom with spermicide) throughout the study period and 7 months after discontinuation of study drug.
  • Non-metastatic, unilateral, newly diagnosed, operable early breast cancer (EBC) of clinical stage II and III including inflammatory breast cancer. Histologically confirmed primary invasive carcinoma of the breast.

Who cannot join

  • 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).
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  • 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
  • high-risk uncontrolled arrhythmias.
  • Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary oxygen therapy.
  • Known history of active hepatitis B virus (HBV) and active hepatitis C virus (HCV) infection.
  • Known HIV infection by patient declaration.
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
  • Known hypersensitivity to the IMPs, non-IMPs or any of the ingredients or excipients of the IMPs or non-IMPs.
  • Known hypersensitivity to murine proteins.
  • Pre-existing peripheral sensory or motor neuropathy ≥ grade 2 (as defined by NCI-CTCAE v4.03).
  • Lactating or pregnant woman. A pregnancy test is required for all women of childbearing potential including women who had menopause onset within 2 years prior to randomisation. Women of childbearing potential must agree to use contraceptive methods during the study and for 7 months after the last dose of IMP.
  • Participation in any clinical study or having taken any investigational therapy during the 1-month period immediately preceding administration of the first dose.
  • Patients unwilling to follow the study requirements.

Trial locations and contacts

15 sites in 13 countries.

15 sites in 13 countries

Hungary2 sites
  • National Institute of Oncology

    Budapest, 1122

  • University of Debrecen

    Debrecen, 4032

Other trials in Hungary

Malaysia2 sites
  • Beacon International Specialist Centre

    Kuala Lumpur, 46050

  • Hospital Kuala Lumpur

    Kuala Lumpur, 50586

Other trials in Malaysia

Belarus1 site
  • Minsk Clinical Oncological Dispensary

    Minsk, 220013

Other trials in Belarus

Bulgaria1 site
  • Complex Oncology Center

    Plovdiv, 4002

Other trials in Bulgaria

Estonia1 site
  • East Tallinn Central Hospital

    Tallinn, 10138

Other trials in Estonia

France1 site
  • Centre René Huguenin (Institut Curie)

    Saint-Cloud, 92210

Other trials in France

Georgia1 site
  • S. Khechinashvili University Hospital

    Tbilisi, 0179

Other trials in Georgia

Italy1 site
  • Modena Hospital

    Modena, 41124

Other trials in Italy

Poland1 site
  • Szpital Specjalistyczny Brzeziny

    Brzeziny, 95-060

Other trials in Poland

Russia1 site
  • LLC "Vitamed"

    Moscow, 129515

Other trials in Russia

Spain1 site
  • Hospital Universitario Virgen Macarena

    Seville, 41009

Other trials in Spain

Thailand1 site
  • Maharaj Nakorn Chiang Mai Hospital

    Chiang Mai, 50200

Other trials in Thailand

Ukraine1 site
  • GI "V. T. Zaycev Institute General and Urgent Surgery of NAMS of Ukraine "

    Kharkiv, 61018

Other trials in Ukraine

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
HD201, Herceptin, Docetaxel, Epirubicin, Cyclophosphamide
Keywords
randomized, double-blind, parallel group, equivalence, multicentre, phase III, efficacy, safety, pharmacokinetics, HD201, docetaxel, Herceptin, HER2 positive, breast cancer, early breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HD201Drug

    Also called Trastuzumab

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

  • HerceptinDrug

    Also called Trastuzumab

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

  • DocetaxelDrug

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

  • EpirubicinDrug

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

  • CyclophosphamideDrug

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

Study groups in NCT03013504
Study groupRoleWhat they receive
HD201 in combination with docetaxelExperimental8 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
Receives: Drug: HD201; Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide
Herceptin® in combination with docetaxelActive comparator8 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
Receives: Drug: Herceptin; Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: After 24 weeks (end of cycle 8)

Secondary outcomes (10)
  1. total breast pathological complete response rate (bpCR)

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

    Measured: After 24 weeks (end of cycle 8)

  2. Overall response rate (ORR)

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

    Measured: After 24 weeks (end of cycle 8)

  3. Overall Survival (OS)

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

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

  4. Event-free Survival (EFS)

    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.

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

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

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

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

  6. Cardiac dysfunction

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

    Measured: Within 28 days before start of treatment, before cycle 5,12 and 16 (1 cycle is 3 weeks), before surgery (after 24 weeks), at end of treatment (4 weeks from last administration of drug medication) and one year after completion of trastuzumab therapy.

  7. Immunogenecity

    Incidence of human trastuzumab antibodies

    Measured: At baseline (within 28 days before start of treatment), before surgery (after 24 weeks), at end of treatment (4 weeks from last administration of drug medication) and one year after completion of trastuzumab therapy.

  8. Clearance (Pharmacokinetic)

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

    Measured: Before administration of treatment at Cycles 5 and 8 (1 cycle is 3 weeks)

  9. Area under the curve (AUC, Pharmacokinetic)

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

    Measured: Before administration of treatment at Cycles 5 and 8 (1 cycle is 3 weeks)

  10. Plasma half life (Pharmacokinetic)

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

    Measured: Before administration of treatment at Cycles 5 and 8 (1 cycle is 3 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2017 (estimated)
  2. Study start19 Feb 2018
  3. Primary completion19 Apr 2019
  4. Study completion13 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
503 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03013504
Sponsor's protocol ID
TROIKA
Acronym
TROIKA
Status last verified
Feb 2023
First submitted
29 Dec 2016
Last updated
6 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36721174
  • 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.

    PubMed 35238873

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing HD201, Herceptin and Docetaxel in people with HER2 Positive Breast Cancer, run by Prestige Biopharma Limited at 15 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Hungary, Malaysia, Belarus, Bulgaria, Estonia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

total pathological complete response rate (tpCR) (time frame: After 24 weeks (end of cycle 8)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03013504, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2024.

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