A Phase I, Open-label, Study of the Safety, Pharmacokinetics, and Pharmacodynamics Dose Escalation of Pazopanib in Combination With Epirubicin or Doxorubicin for Advanced Solid Tumors
- 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
- 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.
- 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
- Any unstable or serious concurrent condition (e.g., active infection requiring
- QTc > 480 msecs.
- History of any one or more of the following cardiovascular conditions within the past
- 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
- 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
- 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