EXTENT: Exemestane With Sunitinib (SUTENT®) in Metastatic Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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:
-
Obtain assessments of overall response rate (ORR), clinical benefit rate (CBR), and overall survival (OS).
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Determine the safety and tolerability of the combination regimen.
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Study molecular changes in tissue biopsies, circulating tumor cells (CTCs), and circulating endothelial cells (CECs), and explore associations with treatment response and resistance.
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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.
-
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Exemestane plus Sutent All patients enrolled on the study will receive treatment as follows: Exemestane 25 mg by mouth every day. Sunitinib 37.5 mg by mouth every day. |
Drug: Exemestane
Exemestane 25 mg by mouth every day.
Other Names:
Drug: Sutent
Sunitinib 37.5 mg by mouth every day.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Must have metastatic breast cancer or locally advanced not amenable to curative therapy.
-
Measurable or evaluable disease are eligible.
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Tumors must be Estrogen Receptor (ER)-positive and/or Progesterone Receptor (PR)-positive.
-
Human Epidermal Growth Factor Recepter 2 (HER2)-positive tumors are allowed but must have failed Herceptin therapy.
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Postmenopausal
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No more than 3 lines of chemotherapy
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No more than 3 lines of hormonal therapy
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Bisphosphonates may be given according to their product license
-
Left ventricular ejection fraction within institutional normal limits
-
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.
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Adequate blood counts
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Normal thyroid function tests.
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Patients with Central Nervous System (CNS) metastatic disease are allowed if the disease is stable for more than 3 months by CT or MRI.
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Adequate general health (Eastern Cooperative Oncology Group (ECOG) performance status 0-2).
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Able to give informed consent and follow the procedures of the study.
Exclusion Criteria:
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Patients previously treated with exemestane in any setting.
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Patients previously treated with sunitinib.
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Patients with cardiac dysfunction or active cardiac disease
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Patients with uncontrolled CNS metastasis.
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Poorly controlled hypertension
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Blood counts or liver and kidney tests that fall outside the ranges outlined in inclusion criteria 9-10 above.
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ECOG performance status 3 or 4.
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History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma of the skin.
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History of a cerebrovascular accident, non-catheter related deep vein thrombosis, or pulmonary embolism in the last 5 years.
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Major surgical procedure or significant traumatic injury within 28 days prior to study entry.
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Premenopausal status.
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History of receiving any investigational treatment within 28 days of study medication initiation.
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Current known infection.
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Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
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Medical or psychiatric condition that in the opinion of the principal investigator impair their ability to participate in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Baylor College of Medicine, Lester and Sue Smith Breast Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Baylor Breast Care Center
- Pfizer
Investigators
- Principal Investigator: Mothaffar Rimiawi, MD, Baylor College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H 24786 / EXTENT
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Exemestane Plus Sutent |
|---|---|
| Arm/Group Description | All patients enrolled on the study will receive treatment as follows: Exemestane 25 mg by mouth every day. Sunitinib 37.5 mg by mouth every day. |
| Period Title: Overall Study | |
| STARTED | 4 |
| COMPLETED | 2 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Exemestane Plus Sutent |
|---|---|
| Arm/Group Description | All patients enrolled on the study will receive treatment as follows: Exemestane 25 mg by mouth every day. Sunitinib 37.5 mg by mouth every day. |
| Overall Participants | 4 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
4
100%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
100%
|
| Male |
0
0%
|
Outcome Measures
| Title | Time to Disease Progression in Weeks |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 patients developed disease progression. |
| Arm/Group Title | Exemestane Plus Sunitinib |
|---|---|
| Arm/Group Description | All patients enrolled on the study will receive treatment as follows: Exemestane 25 mg by mouth every day. Sunitinib 37.5 mg by mouth every day. |
| Measure Participants | 2 |
| Mean (Full Range) [week] |
11.1
|
| Title | Obtain Assessments of Overall Response Rate, Clinical Benefit Rate, and Overall Survival |
|---|---|
| Description | |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Exemestane Plus Sunitinib |
|---|---|
| Arm/Group Description | This is a single arm study. All patients received Exemestane 25mg per day and Sunitinib 37.5 mg per day. |
| Measure Participants | 4 |
| Number [paticipants] |
NA
|
| Title | Determine the Safety and Tolerability |
|---|---|
| Description | |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Exemestane Plus Sunitinib |
|---|---|
| Arm/Group Description | This is a single arm study. All patients received Exemestane 25mg per day and Sunitinib 37.5 mg per day. |
| Measure Participants | 4 |
| Count of Participants [Participants] |
NA
NaN
|
| Title | Study Molecular Changes in Tissue Biopsies, Circulating Tumor Cells, and Circulating Endothelial Cells |
|---|---|
| Description | |
| Time Frame | 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Exemestane Plus Sunitinib |
|---|---|
| Arm/Group Description | This is a single arm study. All patients received Exemestane 25mg per day and Sunitinib 37.5 mg per day. |
| Measure Participants | 4 |
| Median (95% Confidence Interval) [cell] |
NA
|
Adverse Events
| 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. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Exemestane Plus Sutent | |
| Arm/Group Description | All patients enrolled on the study will receive treatment as follows: Exemestane 25 mg by mouth every day. Sunitinib 37.5 mg by mouth every day. | |
All Cause Mortality |
||
| Exemestane Plus Sutent | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Exemestane Plus Sutent | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | |
| Metabolism and nutrition disorders | ||
| Hypertriglyceridaemia | 1/4 (25%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Exemestane Plus Sutent | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | |
| Blood and lymphatic system disorders | ||
| leukopenia | 4/4 (100%) | 4 |
| Hemoglobin | 1/4 (25%) | 1 |
| platelets | 2/4 (50%) | 2 |
| Cardiac disorders | ||
| Hypertension | 3/4 (75%) | 4 |
| Endocrine disorders | ||
| Thyroid function, low | 2/4 (50%) | 2 |
| Eye disorders | ||
| Ocular/Visual | 1/4 (25%) | 1 |
| Gastrointestinal disorders | ||
| Mucositis/stomatitis | 2/4 (50%) | 2 |
| General disorders | ||
| Fatigue | 1/4 (25%) | 1 |
| pain | 1/4 (25%) | 2 |
| Metabolism and nutrition disorders | ||
| AST, SGOT(serum glutamic oxaloacetic transaminase) | 1/4 (25%) | 1 |
| Alkaline phosphatase | 1/4 (25%) | 1 |
| Nervous system disorders | ||
| Dizziness | 1/4 (25%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Dermatology/Skin | 2/4 (50%) | 2 |
| Rash: acne/acneiform | 2/4 (50%) | 2 |
| Vascular disorders | ||
| Thrombosis/embolism | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Mothaffar Rimawi |
|---|---|
| Organization | Baylor College of Medicine |
| Phone | 713-798-1311 |
| rimawi@bcm.edu |
- H 24786 / EXTENT