A phase III randomized trial of trastuzumab continuation vs discontinuation in combination with 2nd-line chemotherapy after progression on a 1st-line trastuzumab-chemotherapy combination for HER2 overexpressing metastatic breast cancer patients. - THOR
- Conditions
- Metastatic breast cancerMedDRA version: 6.1Level: PTClassification code 10055113
- Registration Number
- EUCTR2006-000703-42-IT
- Lead Sponsor
- ROCHE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- Not specified
Patients must show their willingness to participate in the study and comply with its procedures by signing a written informed consent.
Documented diagnosis of metastatic breast carcinoma (stage IV) HER2 overexpressing (ICH 3+ or FISH +).
Progressive disease after 1st line Herceptin+chemotherapy combination (previous hormonal therapies without trastuzumab for metastatic disease are allowed).
Patients must have received as 1st line chemotherapy no other drugs than taxanes, vinorelbine, capecitabine, gemcitabine, platinum compounds, fluorouracil, cyclophosphamide, methotrexate always in association with Herceptin
Age >18
Female gender.
ECOG performance status 0-1 (see Appendix 1).
Life expectancy > 3 months.
Neutrophils > 1.5x109/L and platelets > 100x109/L.
Total bilirubin < 1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT and/or ALAT < 2.5 UNL, alkaline phosphatase < 5 UNL (unless bone metastasis are present in the absence of any liver disorders). Creatinine < 1.5 UNL
At least one measurable leasion according to Recist criteria (max diameter > 2 cm if conventionally measure or > 1 cm if assessed by spiral TC, see Appendix 2)
Complete work-up within 3 weeks prior to registration, including total body CT scan (torax,abdomen, pelvis) or MRI, cardiologic evaluation by echocardiogram or MUGA scan and ECG and complete hematological and biological work-up
LVEF > 50% as determined by echocardiogram or MUGA scan
Women of child bearing potential must have a negative serum pregnancy test and be using adequate contraception (prescribed under medical supervision). Examples of adequate contraceptive measures are intra-uterine device, barrier method (condoms, diaphragm), also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not indicated in this patient population!
Patients must be accessible for treatment and follow-up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
No hormonal and antracyclines regimens are allowed, except pegylated liposomal doxorubicin (pegylated and not) as previous 1st line chemotherapy associated to Herceptin Serious illness or medical condition: - Congestive hearth failure or angina pectoris even if it is medically controlled. - Previous history of myocardial infarction, uncontrolled high-risk ipertension or arrhythmia. - History of significant neurological or psychiatric disorders including dementia or seizures. - Active infection, active peptic ulcer, unstable diabetes mellitus or contraindications for the use of steroids. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening. Occurrence of cardiac toxicity during 1st line Herceptin+chemotherapy treatment defined as follows: - a fall from baseline resting LVEF of 20% or more EF units (LVEF should be reassessed within one week to confirm the diagnosis) - signs and symptoms of CHF classified as grade III or more according to NYHA classification (see Appendix 3). Patients with symptomatic brain metastases. Patients with bone as just one site of metastases. Patients with brain as just one progression site to the 1st line trastuzumab-chemotherapy combination. Patients not receiving suggested regimens as 2nd line chemotherapy (see table 6 for a list of suggested chemotherapy regimens.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare progression free survival in patients with metastatic breast cancer overexpressing HER2 treated with Herceptin and 2nd line chemotherapy beyond first progression versus 2nd line chemotherapy alone. combination.;Secondary Objective: To compare response rate To compare the survival To assess the safety.;Primary end point(s): PFS (Progression-Free Survival)assessment as determined by: - Breast cancer recurrence (assessed by CT or MRI scans, Xray, bone scan, physical examination) - Second primary cancer (contralateral breast or non-breast malignancy) - Death from any cause as first event. OS as determined by death from any cause.
- Secondary Outcome Measures
Name Time Method