This is a study of the effects of CT-P6 and Herceptin in patients with metastatic breast cancer. Patients with metastatic breast cancer who agree to be in this study will receive either CT-P6 or Herceptin in combination with paclitaxel.
- Conditions
- Metastatic breast cancerMedDRA version: 16.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-014463-39-BG
- Lead Sponsor
- Celltrion, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 170
1. Written and signed informed consent, obtained prior to starting any protocol-specific procedures.
2. Are females over 18 years of age.
3. Have pathologically confirmed, uni-dimensionally measurable metastatic breast
cancer.
4. Have a strong Her-2 over-expression as described by a 3+ score by immunohistochemistry (IHC) or a positive fluorescence in-situ hybridisation (FISH) or chromogenic in-situ hybridisation (CISH) result.
5. Have target lesions outside prior radiation fields.
6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Have at least 4 weeks since last surgery or radiation therapy, with full recovery.
Patients must have received no radiotherapy for the treatment of metastatic disease.
However, patients who have received adjuvant radiotherapy as part of the treatment of early breast cancer
are eligible if the last fraction of radiotherapy was administered at least 6 months prior to randomisation.
Radiotherapy administered
for the relief of metastatic bone pain other than the sole site of measurable diseases
is allowed, but:
o no more than 25% of marrow-bearing bone should have been irradiated,
o the last fraction of radiotherapy should not have been administered within
4 weeks prior to randomisation,
o patients must have recovered from all treatment-related toxicities prior to
randomisation.
8. Regarding trastuzumab treatment;
o Have never been treated with trastuzumab, or
o Prior trastuzumab and chemotherapy (taxane included) or trastuzumab alone as
neoadjuvant/adjuvant treatment is discontinued >12 months prior to randomisation.
9. Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first
dose of randomised therapy. Prophylactic use of
bisphosphonates in patients without bone diseases is not permitted, except for the
treatment of osteoporosis.
10. Laboratory requirements as defined below:
Haematology: Absolute neutrophil count (ANC): = 1,500/mm EXP 3 (1.5 x 10 EXP 9 cells/L); Platelets: =
100,000/mm EXP 3 (100 x 10 EXP 9 cells/L); Haemoglobin:
= 9.0 g/dL;
Liver function: Total bilirubin: = 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT): = 2.5 x ULN, or = 5.0 x ULN in the case of liver metastasis;
Renal function: Serum creatinine: =2 mg/dL
11. Are expected to survive for at least 6 months.
12. Are not pregnant and do not plan to become pregnant during the study.
For females of childbearing potential, pregnancy tests must be performed via serum
pregnancy test at baseline (within 7 days prior to starting study drug) and at the end
of treatment. Further tests are only required if there is a suspicion of pregnancy. If
sexually active, must be using at least one reliable method of contraception (e.g., a
barrier method [condom or occlusive cap] with spermicidal
foam/gel/film/cream/suppository, an intrauterine device [IUD] or intrauterine
system [IUS], oral or injectable contraception, sterilisation of sole male partner,
abstinence) throughout the study period and for 6 months after the last study drug
treatment.
Non-childbearing potential is defined as:
- aged =50 years and naturally amenorrhoeic for at least 1 year*, or
- premature ovarian failure confirmed by a specialist gynaecologist, or
- previous bilateral salpingo-oophorectomy or hysterectomy, or
- XY genotype, Turner’s syndrome, uterine agenesis.
* Amenorrhoea following cancer therapy does not rule out childbearing potential.
Are the tri
1. Have received prior chemotherapy for metastatic breast cancer.
2. Current clinical or radiographic evidence of central nervous system (CNS)
metastases. A computerised tomography (CT) or magnetic resonance imaging
(MRI) scan of the brain is mandatory in cases of clinical suspicion of brain
metastases within 21 days of randomisation. Eligible patients must be
asymptomatic and cannot be receiving steroids.
3. Are receiving concurrent immunotherapy or hormonal therapy.
4. Have a history of congestive heart failure (CHF) of any New York Heart
Association (NYHA) criterion, or serious cardiac arrhythmia requiring treatment
(except for atrial fibrillation and/or paroxysmal supraventricular tachycardia).
5. Have an abnormal LVEF (=50%) at baseline, as determined by either
two-dimensional echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
scan. If the patient is randomised, the same method of LVEF assessment, ECHO
or MUGA, must be used throughout the study.
6. History of myocardial infarction within 6 months before randomisation.
7. Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or
diastolic blood pressure >100 mmHg), or unstable angina.
8. Have severe dyspnoea at rest due to complications of advanced malignancy or
requiring supplementary oxygen therapy.
9. Have had a prior malignancy within the last 5 years that might affect breast
cancer diagnosis or assessment.
10. Have had prior mediastinal irradiation (except internal mammary-node irradiation
for the present breast cancer).
11. Have received cumulative doses of anthracycline exceeding 360 mg/m2 of body
surface area for doxorubicin, 720 mg/m2 for epirubicin, 120 mg/m2 for
mitoxantrone, 90 mg/m2 for idarubicin, or the equivalent of 360 mg/m2 of
doxorubicin for other anthracyclines such as liposomal doxorubicin. If more than
one anthracycline has been used, then the cumulative dose must not exceed the
equivalent of 360 mg/m2 of doxorubicin.
12. Have a history of hypersensitivity to the trastuzumab or to drugs with similar
chemical structures, or to any of the excipients, or to murine proteins.
13. Have a history of severe hypersensitivity reaction to paclitaxel, or to any of the
excipients.
14. Have peripheral neuropathy of grade 2 or greater
15. Have active or uncontrolled infection
16. Have any other medical or psychiatric condition that could compromise study
participation.
17. Have received treatment with any other investigational drug in the last 30 days
before study entry, or within less than five half-lives after receiving the previous
investigational drug.
18. Current known infection with human immunodeficiency virus (HIV), hepatitis B
virus (HBV) or hepatitis C virus (HCV).
19. Are pregnant or a nursing mother.
20. Have a history or suspicion of unreliability, poor cooperation or non-compliance
with medical treatment.
21. Have any concurrent disease or condition that, in the opinion of the investigator,
would make the patient unsuitable for participation in the study.
22. Have previously been randomosed in this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to demonstrate equivalent PK in terms of area under the curve at steady state(AUCSS) between CT-P6 and the comparator Herceptin in patients with metastatic breast cancer.;Secondary Objective: The secondary objective is to obtain additional comparative PK data, as well as initial safety and efficacy data with CT-P6 in comparison to Herceptin in patients with metastatic breast cancer.<br>The PK, PD, efficacy and safety objectives are to evaluate CtroughSS, change from baseline in serum Her-2 shed antigen, ORR, cardiotoxicity, and immunogenicity of CT-P6 compared to Herceptin.;Primary end point(s): Pharmacokinetic Analysis: The primary PK endpoint will be the AUCss following steady state. AUCss is defined as the AUC at steady state.;Timepoint(s) of evaluation of this end point: The primary endpoint will be reached at 6 months of treatment (8 treatment cycles).
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Pharmacokinetic Analysis: Trough concentration at steady state (CtroughSS);Timepoint(s) of evaluation of this end point: As per protocol