Breast Neoplasms, Neoplasm Metastasis
Conditions
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.
Interventions
DRUGitraconazole
oral itraconazole 200mg a day until disease progression or unacceptable toxicities.
Sponsors
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Oral Itraconazole | pre-dose at Weeks 2 and 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events Grade 3 or 4 That Are Related to Study Treatment | up to 100 months | 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. |
| Time to Progression. | up to 100 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Itraconazole oral itraconazole 200mg a day until disease progression or unacceptable toxicities. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression, refractory | 1 |
| Overall Study | Disease progression, relapse | 11 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Itraconazole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 3 / 13 |
Outcome results
Primary
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.
Time frame: pre-dose at Weeks 2 and 4
Population: All patients with results available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Itraconazole | Pharmacokinetics (PK) of Oral Itraconazole | Week 2 Intraconazole Concentration | 230.7 ng/mL | Standard Deviation 216.8 |
| Itraconazole | Pharmacokinetics (PK) of Oral Itraconazole | Week 4 Intraconazole Concentration | 305.8 ng/mL | Standard Deviation 334.8 |
| Itraconazole | Pharmacokinetics (PK) of Oral Itraconazole | Week 2 6-OH Itraconazole Concentration | 454.8 ng/mL | Standard Deviation 429.3 |
| Itraconazole | Pharmacokinetics (PK) of Oral Itraconazole | Week 4 6-OH Itraconazole Concentration | 501.6 ng/mL | Standard Deviation 502.6 |
Secondary
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.
Time frame: up to 100 months
Population: All patients in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Itraconazole | Number of Patients With Adverse Events Grade 3 or 4 That Are Related to Study Treatment | 2 Participants |
Secondary
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.
Time frame: up to 100 months
Population: All patients in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Itraconazole | Time to Progression. | 1.54 Months |