Metastatic Breast Cancer
Conditions
Keywords
Breast Cancer, Metastatic, Hormone Receptor Positive
Brief summary
The investigators want to find out if the treatments used in this study are helpful to patients that are diagnosed with hormone receptor positive metastatic breast cancer. The investigators want to also look at any side effects that could happen while patients are on the study treatments. The investigators want to see if there are any changes that could show us if your cancer is responding to the study treatments.
Detailed description
The study design is a phase II design. Eligible patients will undergo staging work up and start treatment. Every 28-day period (4 weeks) will count as a cycle. Medical evaluations will be performed every 4 weeks and staging work up will be repeated every 12 weeks. The primary objective of the study is to assess progression free survival (PFS) of treatment with exemestane and sunitinib in post¬menopausal subjects with hormone receptor positive (ER-positive and/or PR-positive) unresectable locally advanced or metastatic breast cancer subjects who have progressed on prior hormonal treatment. In addition we want to: 1. Obtain assessments of overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS). 2. Determine the safety and tolerability of the combination regimen. 3. Study molecular changes in tissue biopsies, circulating tumor cells (CTCs), and circulating endothelial cells (CECs), and explore associations with treatment response and resistance. 1\. Blood samples will be drawn for enumeration and profiling of circulating tumor cells and circulating endothelial cells at study entry (prior to starting study medications), four weeks after starting study medications, twelve weeks after starting study medications and at disease progression. These samples will be strongly encouraged but the patients may decline any or all of them without impacting their eligibility or continuation on the study. 2\. If the patient participating on the study has an easily accessible breast mass or metastatic lesion (e.g. lymphadenopathy, skin metastasis, chest wall metastasis), a core needle or punch biopsy will be obtained at study entry (prior to starting study medications), four weeks after starting study medications, and at disease progression. These biopsies will be strongly encouraged but the patients may decline any or all of them without impacting their eligibility or continuation on the study.
Interventions
DRUGExemestane
Exemestane 25 mg by mouth every day.
DRUGSutent
Sunitinib 37.5 mg by mouth every day.
Sponsors
Pfizer
Baylor Breast Care Center
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
1. Must have metastatic breast cancer or locally advanced not amenable to curative therapy. 2. Measurable or evaluable disease are eligible. 3. Tumors must be Estrogen Receptor (ER)-positive and/or Progesterone Receptor (PR)-positive. 4. Human Epidermal Growth Factor Recepter 2 (HER2)-positive tumors are allowed but must have failed Herceptin therapy. 5. Postmenopausal 6. No more than 3 lines of chemotherapy 7. No more than 3 lines of hormonal therapy 8. Bisphosphonates may be given according to their product license 9. Left ventricular ejection fraction within institutional normal limits 10. Liver function and kidney function tests within the upper limit of normal. In patients with liver metastasis, liver function tests should be \< 5 times the upper limit of normal. 11. Adequate blood counts 12. Normal thyroid function tests. 13. Patients with Central Nervous System (CNS) metastatic disease are allowed if the disease is stable for more than 3 months by CT or MRI. 14. Adequate general health (Eastern Cooperative Oncology Group (ECOG) performance status 0-2). 15. Able to give informed consent and follow the procedures of the study.
Exclusion criteria
1. Patients previously treated with exemestane in any setting. 2. Patients previously treated with sunitinib. 3. Patients with cardiac dysfunction or active cardiac disease 4. Patients with uncontrolled CNS metastasis. 5. Poorly controlled hypertension 6. Blood counts or liver and kidney tests that fall outside the ranges outlined in inclusion criteria 9-10 above. 7. ECOG performance status 3 or 4. 8. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma of the skin. 9. History of a cerebrovascular accident, non-catheter related deep vein thrombosis, or pulmonary embolism in the last 5 years. 10. Major surgical procedure or significant traumatic injury within 28 days prior to study entry. 11. Premenopausal status. 12. History of receiving any investigational treatment within 28 days of study medication initiation. 13. Current known infection. 14. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures). 15. Medical or psychiatric condition that in the opinion of the principal investigator impair their ability to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression in Weeks | Medical evaluation every 4 weeks;The study does not have a fixed time frame for each participant. Duration of therapy depends on individule response, evidence of disease progression and tolerance | Time from the first day of treatment to date of progression in weeks |
Secondary
| Measure | Time frame |
|---|---|
| Obtain Assessments of Overall Response Rate, Clinical Benefit Rate, and Overall Survival | 5 years |
| Determine the Safety and Tolerability | 5 years |
| Study Molecular Changes in Tissue Biopsies, Circulating Tumor Cells, and Circulating Endothelial Cells | 5 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exemestane Plus Sutent All patients enrolled on the study will receive treatment as follows:
1. Exemestane 25 mg by mouth every day.
2. Sunitinib 37.5 mg by mouth every day. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Exemestane Plus Sutent |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Sex: Female, Male Female | 4 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 | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Time to Disease Progression in Weeks
Time from the first day of treatment to date of progression in weeks
Time frame: Medical evaluation every 4 weeks;The study does not have a fixed time frame for each participant. Duration of therapy depends on individule response, evidence of disease progression and tolerance
Population: 2 patients developed disease progression.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exemestane Plus Sunitinib | Time to Disease Progression in Weeks | 11.1 week |
Secondary
Determine the Safety and Tolerability
Time frame: 5 years
Population: The study was terminated early before target accrual. 4 patients were enrolled and received treatment. 2 patients developed progression and 2 patients was drop-off the study due to adverse events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Exemestane Plus Sunitinib | Determine the Safety and Tolerability | NA Participants |
Secondary
Obtain Assessments of Overall Response Rate, Clinical Benefit Rate, and Overall Survival
Time frame: 5 years
Population: The study was terminated early before target accrual. 4 patients were enrolled and received treatment. 2 patients developed progression and 2 patients was drop-off the study due to adverse events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane Plus Sunitinib | Obtain Assessments of Overall Response Rate, Clinical Benefit Rate, and Overall Survival | NA paticipants |
Secondary
Study Molecular Changes in Tissue Biopsies, Circulating Tumor Cells, and Circulating Endothelial Cells
Time frame: 5 years
Population: The study was terminated early before target accrual. 4 patients were enrolled and received treatment. 2 patients developed progression and 2 patients was drop-off the study due to adverse events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane Plus Sunitinib | Study Molecular Changes in Tissue Biopsies, Circulating Tumor Cells, and Circulating Endothelial Cells | NA cell |