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

• Register: ClinicalTrials.gov
• Last refreshed on: 20 February 2023
• Main ID: NCT03013504
• Date of registration: 29/12/2016
• Prospective Registration: Yes
• Primary sponsor: Prestige Biopharma Limited
• Public title: A Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in HER2+ Early Breast Cancer Patients TROIKA
• Scientific 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
• Date of first enrolment: February 19, 2018
• Target sample size: 503
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03013504
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Belarus, Bulgaria, Czechia, Estonia, France, Georgia, Hungary, Italy, Korea, Republic of, Malaysia, Philippines, Poland, Russian Federation, Spain, Thailand, Ukraine

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Able and willing to give written informed consent.

2. Females = 18 years of Age

3. Eastern Cooperative Oncology Group (ECOG) performance Status (PS) < 2.

4. Known Hormone receptor (oestrogen receptor and progesterone receptor) status.

5. HER2 overexpressed as assessed by

1. Immunohistochemistry (IHC) or

2. Fluorescent in situ hybridisation (FISH); FISH positive is defined as FISH
amplification Ratio = 2.0 / number of HER2 gene copies per cell >2

3. Chromogenetic in stu hybridisation (CISH) positive

4. Patients with IHC score 3+ or positive FISH/CISH test

5. Patients with an IHC score 2+ must also have a positive FISH/CISH test

6. LVEF = 50% or within the normal Level of the Institution, as assessed by
echocardiography or MUGA scan.

7. Life expectancy > 12 weeks.

8. Adequate bone marrow function as evidenced by the following:

1. Absolute neutrophils count = 1,500/µL

2. Haemoglobin = 9 g/dL

3. Platelet count = 100,000/µL Up to 5% Deviation is acceptable.

9. Adequate hepatic and renal function as evidenced by the following:

1. Creatinine clearance = 60mL/min

2. total Bilirubin = 1.5x upper limit of normal (ULN)

3. AST (SGOT) and ALT (SGPT) = 2.5 x ULN Up to 10% deviation is acceptable.

10. Ability to comply with the study protocol.

11. 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.

12. 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.

Exclusion Criteria:

Patients meeting any of the following criteria must not be enrolled in the study:

1. Metastatic (stage IV) with exception of supraclavicular nodes.

2. Bilateral breast cancer

3. Multicentric breast cancer

4. History of any prior invasive breast carcinoma, except for subjects with a past
history of ductal carcinoma in situ (DCIS) treated with surgery.

5. 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).

6. Previous history of radiation therapy, anti-neoplastic immunotherapy, chemotherapy or
anti-neoplastic biotherapy (including prior HER2 directed therapy).

7. Major surgery within 2 weeks prior to randomisation

8. 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.

9. Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary
oxygen therapy.

10. Known history of active hepatitis B virus (HBV) and active hepatitis C virus (HCV)
infection.

11. Known HIV infection by patient declaration.

12. 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.

13. Known hypersensitivity to the IMPs, non-IMPs or any of the ingredients or excipients
of the IMPs or non-IMPs.

14. Known hypersensitivity to murine proteins.

15. Pre-existing peripheral sensory or motor neuropathy = grade 2 (as defined by NCI-CTCAE
v4.03).

16. 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.

17. Participation in any clinical study or having taken any investigational therapy during
the 1-month period immediately preceding administration of the first dose.

18. Patients unwilling to follow the study requirements.



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

HER2 Positive Breast Cancer

Intervention(s)

Drug: Herceptin

Drug: Docetaxel

Drug: HD201

Drug: Cyclophosphamide

Drug: Epirubicin

Primary Outcome(s)

total pathological complete response rate (tpCR) [Time Frame: After 24 weeks (end of cycle 8)]

Secondary Outcome(s)

Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) [Time Frame: From baseline through study completion until 18 months or until death, whichever came first]

Area under the curve (AUC, Pharmacokinetic) [Time Frame: Before administration of treatment at Cycles 5 and 8 (1 cycle is 3 weeks)]

Event-free Survival (EFS) [Time Frame: From date of randomisation until death from any cause or two years after End of Treatment, whichever comes first]

Cardiac dysfunction [Time Frame: 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.]

Overall response rate (ORR) [Time Frame: After 24 weeks (end of cycle 8)]

Overall Survival (OS) [Time Frame: From date of randomisation until death from any cause or two years after End of Treatment, whichever comes first]

Plasma half life (Pharmacokinetic) [Time Frame: Before administration of treatment at Cycles 5 and 8 (1 cycle is 3 weeks)]

total breast pathological complete response rate (bpCR) [Time Frame: After 24 weeks (end of cycle 8)]

Clearance (Pharmacokinetic) [Time Frame: Before administration of treatment at Cycles 5 and 8 (1 cycle is 3 weeks)]

Immunogenecity [Time Frame: 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.]

Secondary ID(s)

TROIKA

Source(s) of Monetary Support

Please refer to primary and secondary sponsors