Clinical trial NCT04385563: A Study to Evaluate the Efficacy and Safety of the Combination of TQ-B211 Plus Docetaxel in Patients With HER2-positive MBC.
Official title: A Phase III,Randomized,Multicenter,Double-blind Clinical Trail to Evaluate the Efficacy,Safety and Immunogenicity of the Combination of TQ-B211 Plus Docetaxel Versus Herceptin® Plus Docetaxel as First-line Treatment in Patients With HER2-positive MBC.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HER2-positive Metastatic Breast Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-05-13
Enrollment: 338
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy,safety and immunogenicity of TQ-B211 plus docetaxel versus Herceptin® plus docetaxel in Patients with HER2-positive metastatic breast cancer.Trastuzumab plus docetaxel was chosen as the comparator in the control group,as it represents a common first-line treatment option used in HER2+ MBC population in China.


Eligibility criteria: Inclusion Criteria:

* Ability to give written informed consent.
* Age：≥18 and ≤75,female.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；Life expectancy of at least 12 weeks.
* Histologically confirmed diagnosis as her2-positive metastatic or locally recurrent breast cancer that cannot be treated with radical surgery or radiotherapy.
* No prior systematical chemotherapy, biotherapy or molecule-targeted therapy for metastatic breast cance.
* Patients must have a measurable disease according to RECIST v. 1.1 28 days before randomization. (Disease in brain or bone will not be included)
* Left ventricular ejection fraction (LVEF) ≥50 percent (%)
* Blood routine examination should meet the following conditions: Absolute neutrophil count (ANC)≥1.5×109/L Platelets ≥100 x 109/L Hemoglobin ≥90 g/L hemameba≥3.0×109/L )
* Liver function should meet the following conditions:

Total bilirubin ≤1.5x Upper Limit of Normal(ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x ULN if no liver involvement or ≤5x ULN with liver involvement.

-Kidney function should meet the following conditions: Cr (creatinine) ≤1.5x ULN or Ccr (creatinine clearance rate) ≥50 mL/min.

* The coagulation function should meet the following conditions: International normalized ratio（INR）≤1.5；Activated partial thromboplastin time or partial thromboplastin time ≤1.5×ULN
* Female who meet the following criteria can participate in the study:

No childbearing potential； Female with childbearing potential: negative pregnancy test within 7 days before the first administration of the investigational drug; patients are not breastfeeding; Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment.

Exclusion Criteria:

* Not eligible for docetaxel combination therapy.
* Endocrine therapy within 2 weeks before randomization.
* Patients had received neoadjuvant or adjuvant therapy with herceptin 12 months before randomization.
* Patients had received neoadjuvant/adjuvant drugs containing other anthracycline or taxol 6 months before randomization.
* Patients had used Chinese patent medicine or Chinese herbal medicine with anti-cancer activity 2 weeks before randomization.
* Brain metastases with symptom/untreated brain metastases/other central nervous system(CNS) metastases. Treated CNS metastases remain stable for at least 4 weeks before the study, and no evidence of cerebral edema, no sign for glucosinolates or anticonvulsants treatments.
* Patients with a previous malignancy within the past 5 years (other than curatively treated in situ carcinoma of the cervix, non-melanoma skin cancer and superficial bladder carcinoma).
* Hepatitis virus C(HCV) positive, HIV positive, syphilis positive, or HBsAg positive and Hepatitis virus B(HBV) DNA titer in peripheral blood is beyond the normal range.
* Patients had received major surgical procedures (including open chest biopsy) major trauma (e.g. fracture) within 4 weeks before randomization, and there are unhealed wounds, ulcers or fractures at the time of screening or major surgery is expected during the study
* Patients have a history of hypertensive encephalopathy or a hypertension or an uncontrolled hypertension ( systolic blood pressure \>150mmHg or diastolic blood pressure \>100mmHg with antihypertensive drugs)
* Patients had a history of myocardial infarction 6 months before randomization; medical history of congestive heart failure in New York heart association classification (NYHA)≥ grade II,and a severe arrhythmia that cannot be controlled by drugs（atrial fibrillation and paroxysmal supraventricular tachycardia are excluded）;LVEF had previously declined to less than 50% during or after new trastuzumab adjuvant or adjuvant therapy.
* Allergies to herceptin ®/ TQ-B211 or the chemotherapies involved in this trial and their excipients.
* History hypersensitivity to any study drug .
* Patients had participated in clinical trials of other antitumor drugs 4 weeks before randomization .
* Not eligible to join the study judged by investigators.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Baseline up to week 24（Baseline up to 8 cycles）
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: up to week 120
measure: Progression-free survival (PFS)
timeFrame: up to week 120
measure: Disease control rate(DCR)
timeFrame: up to week 120
measure: Overall survival (OS)
timeFrame: up to week 120
Other outcomes:
Locations:
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: