Clinical trial NCT00102895 (phase 2, status: terminated)
Conditions: breast neoplasms, neoplasm metastasis
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: cp-724,714
SMILES: COCC(=O)NC\C=C\C1=CC=C2N=CN=C(NC3=CC=C(OC4=CC=C(C)N=C4)C(C)=C3)C2=C1
Reason stopped: 
    see detailed description
  
Eligibility criteria:

        Inclusion Criteria:

          -  Signed written and voluntary informed consent

          -  Histologically or cytologically confirmed breast cancer

          -  Stage IV (metastatic) breast cancer

          -  Biopsy (fresh or archival) of primary breast cancer or metastatic site demonstrating
             HER2 gene amplification as determined in study-specified central laboratory by
             fluorescence in situ hybridization (FISH)

          -  Prior treatment and progressive disease with at least 1 but not more than 2 cytotoxic
             chemotherapy regimen(s) for metastatic disease

          -  Those for whom the use of an investigational HER2 inhibitor is appropriate because
             they do not have access to approved HER2 inhibitors (e.g., Herceptin®) or for whom
             treatment with currently available HER2 inhibitors is inappropriate

          -  Limited visceral disease burden (i.e., <30% involvement of any organ) and limited
             disease-related symptoms (i.e., well controlled with supportive care measures)

          -  Presence of at least one measurable target lesion [i.e., malignant tumor mass that can
             be accurately measured in at least 1 dimension of >=2 cm with conventional
             radiographic techniques or magnetic resonance imaging, or >=1 cm with spiral CT scan
             as per RECIST], excluding previously irradiated lesions, bone metastasis or pleural
             effusion as sole manifestations of disease. If the measurable disease is restricted to
             a solitary lesion, its neoplastic nature must be confirmed by cytology/histology

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 1

          -  Patient available for treatment, monitoring, and follow-up. Willing and able to comply
             with scheduled visits, therapy plan, laboratory tests and blood sampling for
             pharmacokinetic (PK) analyses

          -  Recovery to baseline or NCI CTCAE Version 3.0 Grade 1 toxicity from all acute effects
             related to prior treatment, except alopecia

          -  Adequate Bone Marrow Function, including: a. Absolute neutrophil count (ANC) >=1500
             cells/mm3; b. Platelets >=100,000 cells/mm3

          -  Adequate Renal Function, including: a. Estimated creatinine clearance >=60 mL/min; b.
             SrCr <1.5 x ULN

          -  Adequate Liver Function, including: a. Bilirubin <=ULN (upper limit of normal); b. AST
             (SGOT) <=2.5 x ULN; c. ALT (SGPT) <=2.5 x ULN

          -  Adequate Cardiac Function, including: a. 12-Lead electrocardiogram (ECG) with normal
             tracing or non clinically significant changes that do not require medical
             intervention; b. QTc interval <=450 msec and without history of Torsades des Pointes
             or other symptomatic QTc abnormality; c. Left ventricular ejection fraction (LVEF) >=
             institutional lower limit of normal and 45% as measured by echocardiogram or multi
             gated radionuclide angiography (MUGA) within 4 weeks prior to start of study treatment

          -  >= 18 years old

          -  Female

        Exclusion Criteria:

          -  Women of child-bearing potential who are unwilling or unable to use an acceptable
             method to avoid pregnancy for the entire study period and up to 4 weeks after study

          -  Women who are pregnant or breastfeeding

          -  Women with a positive pregnancy test on enrollment or within 72 hours prior to study
             drug administration

          -  Prior treatment with trastuzumab (Herceptin®) or other HER2-targeting agents [e.g.,
             lapatinib (GW572016), pertuzumab (Omnitarg™; rhuMab 2C4), CI 1033, EKB 569, CP
             724,714]

          -  Cumulative dose >450 mg/m2 of doxorubicin or doxorubicin equivalents

          -  Prior high-dose chemotherapy requiring hematopoetic stem cell transplantation within
             12 months of study treatment start

          -  Radiotherapy, investigational chemotherapy, biologic therapy within 4 weeks of study
             treatment start

          -  Previous (within the last 5 years) or current malignancies arising from sites other
             than breast, except for adequately treated basal cell or squamous cell skin cancer or
             in situ carcinoma of the cervix uteri

          -  Known or clinically suspected brain metastasis or leptomeningeal disease (no screening
             CT scan required) requiring therapy. Patients with asymptomatic previously treated CNS
             metastases that no longer require therapy or corticosteroids/anticonvulsants for at
             least 4 weeks prior to start of study treatment are eligible

          -  Any clinically significant gastrointestinal abnormalities, which may impair intake,
             transit or absorption of the study drug, such as the inability to take oral medication
             in tablet form, prior complete/partial gastrectomy or intestinal resection, or a
             requirement for H2 antagonists or proton pump inhibitors

          -  Any mental disorder that would limit the understanding or rendering of informed
             consent and/or compromise compliance with the requirements of this protocol

          -  Uncontrolled or significant cardiovascular disease, including: a. Myocardial
             infarction within 12 months; b. Uncontrolled angina within 6 months; c. Congestive
             heart failure within 6 months or left ventricular ejection fraction below local
             institutional lower limit of normal or below 45%; d. Diagnosed or suspected congenital
             long QT syndrome; e. Any history of clinically significant ventricular arrhythmias
             (such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes); f.
             Prolonged QTc interval on pre-entry electrocardiogram (>450 msec); g. Any history of
             second or third degree heart block (may be eligible if currently have a pacemaker); h.
             Heart rate <50/minute on pre-entry electrocardiogram; i. Uncontrolled hypertension

          -  History of drug-induced hyperbilirubinemia

          -  Concurrent treatment with approved or investigational chemotherapy, hormonal therapy,
             immunotherapy, or radiotherapy (hormone replacement therapy is permitted)

          -  Concurrent treatment with H2 antagonists and/or proton pump inhibitors. However, H2
             antagonists can be used for the treatment of an unexpected hypersensitivity reaction
             during the study period. Antacids are allowed but only up to 2 hours before and 2
             hours after study drug administration

          -  Concurrent treatment or treatment within 4 weeks of first dose with potent and/or
             irreversible CYP3A4 inhibitors including: ketoconazole, itraconazole, troleandomycin,
             clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir,
             nefazodone, mibefradil, amiodarone and grapefruit juice

          -  Concurrent treatment or treatment within 4 weeks of first dose with potent inducers of
             CYP3A4 including: rifampin, rifabutin, rifamycins, phenytoin, barbiturates,
             carbamazepine, glucocorticoids, modafinil, phenobarbital, troglitazone, pioglitazone,
             efavirenz, nevirapine, dexamethasone, and St. John's wort

          -  Prisoners or patients who are compulsorily detained or involuntarily incarcerated
             (e.g., for treatment of infectious disease, psychiatric illness, etc.)