Clinical trial NCT00251433 (phase 1, status: active, not recruiting)
Conditions: neoplasms, breast
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: lapatinib, docetaxel, trastuzumab, docetaxel, trastuzumab
SMILES: CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1, [H][C@@]12C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C4=C(C)[C@H](C[C@@](O)([C@@H](OC(=O)C5=CC=CC=C5)[C@]3([H])[C@@]1(CO2)OC(C)=O)C4(C)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be 18 years of age.

        Criteria for female subjects:

          -  Non-child-bearing potential (i.e., women with functioning ovaries who have a current
             documented tubal ligation or hysterectomy, or women who are post- menopausal);

          -  Child-bearing potential (i.e., women with functioning ovaries and no documented
             impairment of oviductal or uterine function that would cause sterility.) This category
             includes women with oligomenorrhoea (severe), women who are perimenopausal, and young
             women who have begun to menstruate. These subjects must have a negative serum
             pregnancy test at screening and agree to one of the following:

          -  Complete abstinence from intercourse from 2 weeks prior to administration of the first
             dose of study medication until 28 days after the final dose of study medication; or

          -  Consistent and correct use of one of the following acceptable methods of birth
             control:

          -  male partner who is sterile prior to the female subject's entry into the study and is
             the sole sexual partner for that female subject; implants of levonorgestrel;
             injectable progestogen; any intrauterine device (IUD) with a documented failure rate
             of less than 1% per year; oral contraceptives (either combined or progestogen only);
             or barrier methods, including diaphragm or condom with a spermicide.

          -  Subjects must have an ECOG Performance Status of 0 to 1.

          -  Subjects must have histologically- or cytologically-confirmed invasive breast cancer
             with Stage IV disease.

          -  Subjects must have measurable lesion(s) according to RECIST criteria for phase II,
             however for phase I subjects evaluable disease will be allowed (including patients
             with bone lesion only disease).

          -  Prior to enrolment in the Phase I part of the study, subjects must have documentation
             of ErbB2 over-expression via IHC3+ or FISH+ testing. Prior to enrolment in the Phase
             II part of the study, subjects must have ErbB2 over-expression confirmed by a central
             laboratory,

          -  Subjects with stable CNS metastases or leptomeningeal involvement are eligible only if
             they are not taking oral steroids or enzyme-inducing anticonvulsants. Subjects with
             CNS only disease will not be allowed.

          -  Subjects that received prior radiotherapy must have completed radiotherapy treatment
             at least 4 weeks before enrolment and recovered from all treatment-related toxicities.

          -  Subjects must have new or archived tumour tissue available prior to study entry to
             evaluate levels of relevant biomarkers.

          -  Subjects must have a cardiac ejection fraction within the institutional range of
             normal as measured by Multigated Acquisition (MUGA) scan or echocardiogram (ECHO).

          -  Subjects must have adequate haematological, hepatic, and renal function. Haemoglobin
             ≥9gm/dL Absolute granulocyte count ≥1500/mm³ (1.5 x 10^9/L) Platelets ≥75,000/mm³ (75
             x 10^9/L) Total bilirubin ≤1.5mg/dL Both ALT and AST ≤1.5 times the upper limit of the
             normal range (ULN) and alkaline phosphatase ≤2.5 times the ULN (See Taxotere Data
             Sheet) Serum creatinine ≤ 2.0mg/dL or calculated creatinine clearance (CrCl) ≥40mL/min
             according to the formula of Cockcroft and Gault

          -  Subjects who received a taxane as part of adjuvant or neoadjuvant therapy are eligible
             if they had progression of their disease more than 6 months after completion of
             treatment.

          -  Subjects who received prior ErbB inhibitors in the adjuvant setting will be allowed,
             but a disease-free interval of at least 6 months must be demonstrated after the end of
             therapy.

        Exclusion Criteria:

          -  Subject has peripheral neuropathy of grade 2 or higher;

          -  Subject has had prior systemic therapy (except one line of hormonal therapy) for
             metastatic disease. Also, any subjects with prior chemotherapy in the adjuvant or
             neoadjuvant setting with anthracycline or anthracenedione-containing regimens with
             cumulative doses of ≥360mg/m² of doxorubicin, ≥720mg/m² of epirubicin, or ≥72mg/m² of
             mitoxantrone;

          -  Subjects with prior systemic investigational drugs within the past 30 days or topical
             investigational drugs within the past 7 days;

          -  Subjects with uncontrolled or symptomatic angina, arrhythmias, or congestive heart
             failure;

          -  Subjects with a known immediate or delayed hypersensitivity or untoward reaction to
             docetaxel, trastuzumab, or other related compounds, or to drugs chemically related to
             lapatinib. These include other aminoquinazolines, such as gefitinib (Iressa),
             erlotinib (Tarceva), or other chemically-related compounds.

          -  Subjects taking any prohibited medications

          -  Subject neither affiliated with, nor beneficiary of a social security category (For
             France only)