Post Menopausal, Hormone Receptor Positive Breast Cancer
Conditions
Keywords
breast cancer, ER positive, PR positive, post menopausal
Brief summary
In this study the investigators want to find out about the effects of this drug in women with metastatic breast cancer. The study has two major parts; dose escalation and dose expansion. In the first part or dose escalation, subjects will be treated at the lowest dose effective in men: 300 mg two times daily. Orteronel (TAK-700) will be increased to reach the highest dose tolerated in men: 400 mg two times daily. This part of the study is designed to see if female subjects can safely tolerate orteronel (TAK-700), and to measure the changes in estrogens and androgens at different levels of TAK-700. In the second part of the study (dose expansion), seven women will be treated with the dose identified in the first part of the study as being safest and most effective. In this part of the study, the investigators want to see if orteronel (TAK-700) will routinely and significantly decrease the estrogen levels at the dose which will be used for any future studies.
Interventions
DRUGTAK700
dose is dependant on dose escalation timepoint and dose expansion cohort dose will be the RP2D determined based on the dose escalation cohort final dose recommendation
Sponsors
Millennium Pharmaceuticals, Inc.
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntary written informed consent * Patients 18 years or older * Screening clinical laboratory values as specified below: * Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be the upper limit of normal (ULN). * Total bilirubin ≤ 1.5 x ULN. * Serum creatinine ≤ 1.5 × ULN or Estimated creatinine clearance using the Cockcroft-Gault formula must be greater than 50 mL/minute * Absolute neutrophil count (ANC) greater than 1000/L and platelet count greater than 75,000/L. * Serum potassium levels must be within institutional normal limits. * Serum magnesium and phosphorous levels must be ≥ the institutional lower limit of normal. * Screening calculated ejection fraction greater than or equal to the institutional upper limit of normal * Patients must have histologically confirmed breast cancer that is Metastatic OR Incurable and locally advanced * Patients must have histologically confirmed HR+ breast cancer. * Patients must have measureable or evaluable disease * ECOG performance status \<2 (Karnofsky \>60%) * Patients must be postmenopausal women. Inclusion Criteria for Dose Expansion Cohort: * All of the criteria listed in above in addition to those below: * Patients must have measurable disease. * Patients may not have received more than 1 prior line of endocrine therapy in the metastatic setting. * Patients may not have received any cytotoxic chemotherapy for treatment in the metastatic setting.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a way to determine the recommended phase 2 dose. | one year | Determine the RP2D of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. |
| decrease in serum estradiol level | one year | To demonstrate clinically significant decrease in serum estradiol following treatment with orteronel at RP2D in postmenopausal women with HR+ metastatic breast cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | one year | Determine toxicity of orteronel in patients being treated at the RP2D |
| response rate, progression-free survival and time to progression | 2 years | To determine the ORR, DCR, progression-free survival (PFS) and time-to-progression (TTP) in HR+ metastatic breast cancer patients receiving orteronel in the dose-expansion cohort |
| pharmacodynamic activity of orteronel with steroid and endocrine levels | two years | Demonstrate the pharmacodynamic activity of orteronel by assessing steroid hormone and other endocrine levels before and following administration of orteronel. |
| Overall Response Rate | one year | Determine the overall response rate (ORR) and disease control rate (DCR) for orteronel in all patients treated with orteronel on protocol |
Other
| Measure | Time frame | Description |
|---|---|---|
| assess changes in serum estrogen, progesterone, androgen and other hormones | 2 years | Assess changes in serum estrogen, progesterone, androgen and other hormones in response to orteronel, and correlate tumor response to orteronel with reduction in serum levels of estrogens and androgens. See Table 4-1 and 4-2 for planned steroid hormone and other endocrine levels. |
| Response to orteronel with AR and ER alpha expression | 2 years | Correlate response to orteronel with tumor expression of androgen receptor (AR), estrogen receptor alpha (ERα), and progesterone receptor (PgR), determined by immunohistochemistry (IHC) in primary and/or metastatic biopsies. |
Countries
United States
Outcome results
None listed