A Pilot Trial of Itraconazole Pharmacokinetics in Patients With Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Cancer cells need to be able to make new blood vessels in order to keep growing. This is called angiogenesis. In a laboratory setting, the drug itraconazole was shown to help stop the growth of new blood vessels (anti-angiogenesis). It is hoped that itraconazole will prevent new blood vessels from forming in humans too. The purpose of this study is to look at how the body processes and breaks down itraconazole (called pharmacokinetics). This study will also measure markers in your blood to see if itraconazole stops new blood vessels from forming. The safety of itraconazole will also be tested to see what effects (good and bad) it has on you and your breast cancer.

Official Title
-----------------
A Pilot Trial of Itraconazole Pharmacokinetics in Patients With Metastatic Breast Cancer

Conditions
-----------------
Breast Neoplasms, Neoplasm Metastasis

Intervention / Treatment
-----------------
* Drug: itraconazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Patients must have a pathologically confirmed diagnosis of invasive carcinoma of the breast. - Patients must carry a diagnosis of metastatic breast cancer. - Patients must be able to swallow oral medications. - Patients with HER 2+ tumors must have received trastuzumab in the past and may have had lapatinib. - Patients must have an ECOG performance status of 0-1. - Patients must be informed of the investigational nature of the study and must sign and give written informed consent. - Patients must have recovered to grade <1 from all acute toxicity of previous therapy for breast cancer with the exception of alopecia. - Adequate hematologic and hepatic function: 1)Absolute neutrophil count >= 1,500 mm3 2) Platelet count >= 100,000 mm3 3) Bilirubin <= 1.5mg/dL x ULN 4) AST and/or ALT <= 2 x ULN (< 5 x ULN in presence of known liver metastasis). - Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and must practice an effective method of birth control. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should also practice an effective method of birth control. - All WOCBP MUST have a negative serum or urine pregnancy test within 4 weeks prior to the start of study drug administration. Exclusion Criteria: Use of the following concomitant medications within 14 days of starting protocol therapy is prohibited: Cisapride, dofetilide, ergot derivatives, levomethadyl, lovastatin, midazolam, pimozide, quinidine, simvastatin, or triazolam. Patients who are taking alprazolam (Xanax) are excluded from the trial. Patients must not have an active infection requiring the use of intravenous antibiotics. The use of oral antibiotics is allowed. Hypersensitivity to itraconazole, any component of the formulation, or to other azoles. Patients with uncontrolled CNS metastasis are excluded. If patients have CNS metastasis they must have completed brain radiation at least 2 weeks prior to registration and must be off steroids for CNS metastasis. Known preexisting congestive heart failure or left ventricular dysfunction. Patients with risk factors (ex. uncontrolled hypertension with BP >160/90) for cardiac dysfunction but no preexisting diagnosis of congestive heart failure or left ventricular dysfunction will have a screening EKG prior to enrollment. Subsequently, those patients with an abnormal EKG, as judged by the treating physician, will be excluded from the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: itraconazole<br>Patients will receive oral itraconazole 200mg a day until disease progression. | Drug: itraconazole<br>* oral itraconazole 200mg a day until disease progression or unacceptable toxicities.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Oral Itraconazole | To determine the pharmacokinetics (PK) of oral itraconazole in patients with MBC by measuring mean trough plasma levels at steady state at weeks 2 and 4. | pre-dose at Weeks 2 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events Grade 3 or 4 That Are Related to Study Treatment | Number of patients with Adverse Events grade 3 or 4 that are related to study treatment. This will look into the safety of the study drug. | up to 100 months | 
| Time to Progression. | This is calculated as time till progression from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months. If a patient did not progress, they were censored at the last evaluation visit. The median time till progression is calculated with its 95% confidence interval. | up to 100 months |