Clinical trial NCT00722293 (phase 1, status: completed)
Conditions: neoplasms, breast
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: doxorubicin, pazopanib (gw786034), epirubicin
SMILES: COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O, CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1, CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must provide written informed consent prior to performance of study specific
             procedures or assessments, and must be willing to comply with treatment and follow up

          -  Histologically or cytologically confirmed diagnosis of advanced solid tumor that has
             failed standard therapy or for which there is no standard therapy and is indicated for
             treatment with anthracyclines.

          -  Age greater than or equal to 18 years.

          -  Adequate organ system function as defined by the protocol.

          -  ECOG performance value of 0 or 1.

          -  Less than or equal to one prior line of chemotherapy for advanced disease. Patients
             with metastatic disease to the brain should have definitive therapy for their brain
             metastases, should be asymptomatic. (Patients with previously treated brain metastases
             who are asymptomatic, off steroids and anti-seizure medications for greater than 3
             months are eligible for the study).

          -  There must be measurable disease or evaluable disease for subjects to be included in
             the cohort expansion phase. Measurable disease is not a criterion for subjects
             enrolling in the dose escalation phase.

          -  Has a left ventricular ejection fraction (LVEF) greater than or equal to 50% or
             greater than or equal to the institution's LLN.

          -  Women of childbearing potential must have a negative pregnancy test within 2 weeks of
             starting study drug and use acceptable birth control methods as outlined in the
             protocol.

          -  Women may participate if they are of non childbearing potential (bilateral tubal
             ligation, hysterectomy, post menopausal or bilateral ovariectomy.

          -  Males with female partners of childbearing potential may participate if they practice
             acceptable methods of birth control as outlined in the study protocol.

          -  Able to swallow and retain oral medications.

          -  Less than or equal to one prior line of chemotherapy for advanced disease.

          -  Life expectancy of at least 12 weeks.

        Exclusion Criteria:

          -  Prior use of pazopanib or prior treatment with anthracyclines. Prior therapy with
             other angiogenesis inhibitors is permitted.

          -  Clinically significant gastrointestinal abnormalities which might interfere with oral
             dosing.

          -  Any unstable or serious concurrent condition (e.g., active infection requiring
             systemic therapy).

          -  QTc > 480 msecs.

          -  History of any one or more of the following cardiovascular conditions within the past
             6 months:

               -  Cardiac angioplasty or stenting

               -  Myocardial infarction

               -  Unstable angina

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure

          -  Any major surgery or trauma within the last 28 days and or presence of non-healing
             wound, fracture, or ulcer.

          -  Any unstable or serious concurrent condition.

          -  Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140mmHg
             or diastolic blood pressure (DBP) of = 90mmHg].

          -  History of cerebrovascular accident (CVA), pulmonary embolism or untreated deep venous
             thrombosis (DVT) within the past 6 months. Subjects with a recent DVT who have been
             treated with therapeutic agents (excluding therapeutic warfarin) for at least 6 weeks
             are eligible.

          -  Prior major surgery or trauma within 28 days prior to first dose of study drug and /or
             presence of any non-healing wound, fracture, or ulcer.

          -  Hemoptysis within 6 weeks prior to first dose of study drug.

          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with patient's safety, provision of informed consent, or compliance to
             study procedures.

          -  Is unable or unwilling to discontinue prohibited medications for 14 days or five
             half-lives of a drug prior to Visit 1 and for the duration of the study.

          -  Use of an investigational agent, including an investigational anti-cancer agent,
             within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study
             drug.

          -  Is now undergoing and/or has undergone within 28 days immediately prior to first dose
             of study drug, any cancer therapy (major surgery, investigational agent, tumor
             embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or
             hormonal therapy).

          -  Clinically assessed as having inadequate venous access for PK sampling.

          -  Lactating and pregnant women should discontinue lactation prior to first use of study
             drug and refrain from nursing throughout the treatment period and for 14 days after
             final dose.