Phase III clinical trial comparing safety and efficacy of BCD-022 (CJSC BIOCAD, Russia) used with paclitaxel to Herceptin® used with paclitaxel in the first-line treatment of HER2 positive metastatic breast cancer patients.
- Conditions
- Health Condition 1: null- Patients with HER2-positive metastatic breast cancer.
- Registration Number
- CTRI/2014/07/004722
- Lead Sponsor
- BIOCAD INDIA PVT LTD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 206
1.Written informed consent and ability to follow the Protocol procedures;
2.Age18 years and age 75 years;
3.Female gender;
4.Histologically confirmed breast cancer (BC);
5.Metastatic BC (stage IV according to TNM classification version 6);
6.Grade 3+ HER2 overexpression confirmed by immunohistochemical (IHC) staining or grade 2+ HER2 overexpression accompanied by HER2 gene amplification confirmed by fluorescent hybridization in situ (FISH) ;
7.Documented results of oestrogen and progesterone receptors expression analysis;
8.ECOG status 0, 1 or 2, not increasing within 2 weeks prior to randomization;
9.Life expectancy â?? 20 weeks or more from the moment of randomization;
10.Presence of at least 1 tumour lesion with a size not less than 1 cm (revealed with CT slice thickness not more than 5 mm). Patients having bone metastasis as the only measurable tumour lesion are not eligible for the trial;
11.Patients of childbearing potential must implement reliable contraceptive measures during the study treatment, starting 4 weeks prior to inclusion into the trial and until 6 months after the last administration of the study drug .
1. Previous anticancer therapy for metastatic BC, including cytotoxic chemotherapy, or previous anticancer therapy with signal transduction inhibitors (e.g. lapatinib), biological drugs (e.g. trastuzumab, bevacizumab), experimental (not approved for BC therapy) anticancer drugs. Any previous hormonal therapy is allowed;
2. Disease progression within 6 months after adjuvant and/or neoadjuvant BC therapy.
3. Surgery, radiation therapy, hormonal therapy, use of any experimental medications within 4 weeks (28 days) prior to randomization.
4. Hypersensitivity to paclitaxel and all medications containing polyoxyethylated castor oil, hypersensitivity to dexamethasone, diphenhydramine, ranitidine/cimetidine, recombinant murine proteins, contrast agents or excipients of study medications;
5. BC metastases in CNS, progressing or clinically manifested (e.g. cerebral oedema, spinal cord injury), with exception of non-progressing metastases not requiring treatment with glucocorticosteroids and/or anticonvulsants within 4 weeks prior to randomization;
6. Cardiovascular system pathology (CHF stage III-IV according to NYHA classification, unstable angina pectoris, myocardial infarction) within 12 months prior to randomization;
7. Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medicamental correction methods (low salt diet, physical exercise);
8. Left ventricular ejection fraction <50% according to ECG;
9. Neutrophils <=1500/mm3;
10. Platelets <=100 000/mm3;
11. Hemoglobin <=90 g/L;
12. Creatinine level >= 1.5 Ã? upper limit of normal (ULN);
13. Bilirubin level >= 1.5 Ã? ULN;
14. AST and ALT levels >= 2.5 Ã? ULN (5 Ã? ULN for patients with liver metastases);
15. Alkaline phosphatase level >= 5 Ã? ULN;
16. Pregnancy or lactation;
17. Any other concomitant cancer including contralateral breast cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
18. Conditions limiting patientâ??s adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
19. Stage II-IV neuropathy according to CTCAE v.4.0;
20. Concomitant participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
21. Acute or active chronic infections;
22. HCV, HBV, HIV or syphilis infections;
23. Obstacles in intravenous administration of study drugs.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The therapy efficacy will be evaluated using contrast-enhanced computed tomography (CT) data. The efficacy analysis will include all randomized evaluable patients (ITT â?? intent-to-treat analysis). Contrast-enhanced CT will be performed at screening, after 3 therapy cycles (21±3 days after 3rd administration of investigational product) and after 6 therapy cycles (21±3 days after 6th administration of investigational product).Timepoint: As defined in protocol
- Secondary Outcome Measures
Name Time Method â?¢Saftey and efficacy evaluation. <br/ ><br>â?¢AE incidence in both groups. <br/ ><br>â?¢Treatment discontinuation due to adverse events. <br/ ><br>â?¢Pharmacokinetics evaluation. <br/ ><br>To evaluate overall response rate <br/ ><br>Timepoint: As defined in protocol